Cytogenetics and Molecular Genetics

Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogénétique hématologique


Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.


The t(8;16)(p11;p13) is a rare translocation (<1% of acute myeloid leukaemia (AML)) involved in de novo and therapy-related myelomonocytic and monocytic acute leukaemia (French-American-British co-operative group (FAB) AML-M4, -M5a and -M5b).1, 2 This abnormality is described at any age and in both sexes. Extramedullary involvement, such as skin or visceral infiltrates, is frequent. Disseminated intravascular coagulation is classically observed.3 Cytology is particular with a noticeable erythrophagocytosis. Phenotypic studies often show CD34−/CD56+ blasts.4 The prognosis of the disease is poor.

The gene involved in 8p11 is MOZ (monocytic leukeamia zinc finger), currently named MYST3 (MYST histone acetyltransferase 3),5 composed of 17 exons. The MYST3 protein is localized in the nucleus, has an histone acetyltransferase activity and acts as a transcriptional regulator.6 The most frequent MYST3 partner gene is CREBBP (CREB-binding protein) in 16p13.5 The CREBBP protein is widely expressed, localized in the nucleus and plays a transcription regulatory role by interaction with the DNA-binding protein CREB.5 Like MYST3, CREBBP has an histone acetyltransferase activity and is essential in embryogenesis, cell differentiation, apoptosis and proliferation.7 Alternative translocations of the t(8;16)(p11;p13) have been reported in few cases, all involving MYST3. The t(8;19)(p11;q13)8 has no identified MYST3 partner gene; the t(8;22)(p11;q13)9 leads to MYST3-EP300 fusion;10 the inv(8)(p11q13)11 to MYST3-NCOA2 fusion12 and the t(8;20)(p11;q13) to MYST3-NCOA3 fusion.13

Symptoms and cytology of AML with MYST3 rearrangement are easily distinguished from the other haematological malignancy associated with 8p abnormality and involving the FGFR1 gene (Fibroblast Growth Factor Receptor 1), which is observed in myeloproliferative disorders and/or mixed T-lymphoma/myeloproliferative disorders.

Translocations involving MYST3 have been described in several reports, but the study of a consequent series of patients has not been done because of the rarity of this abnormality. Here, we describe a multicentric series of 30 cases of MYST3-linked AML. Our objective was to define the most frequent and relevant characteristics of this AML, which seems to define a singular entity by its clinical, cytologic, cytogenetic, molecular and prognostic presentation.

Materials and methods


Fourteen centres in France and Belgium participated in the groupe francophone de cytogénétique hématologique (GFCH) study, which included 30 cases (Table 1), on the basis of an 8p11 abnormality in de novo and therapy-related AML, and excluding T-lymphoid disease or myeloproliferative disorders with adenopathy (FGFR1 involvement). Cases 7 and 8 have been already published.14

Table 1 Characteristics of the 30 patients, previous malignancy and evolution

Morphologic, cytochemic and immunophenotypic analyses

All cases were reviewed by three cytologists (GF, AE and DS) to give a homogeneous response to analysed criteria. Revision was done in Strasbourg and Marseille (France) from blood- and bone marrow-communicated slides and/or teletransmitted images. In one case, (case 25), bone marrow aspiration was not done at diagnosis. Diagnosis classification was made according to the FAB15 and World Health Organization16 classifications including morphologic (acute myelomonocytic leukaemia M4, acute monoblastic leukaemia M5 with a majority of monoblasts M5a or promonocytes M5b), cytochemical, immunophenotypic, genetic and clinical features. We looked for the presence of cytoplasmic vacuoles and erythrophagocytosis (Table 2). Cytochemical analyses were reviewed (peroxidases and esterases) and immunophenotypes established the monocytic differentiation of blasts, when necessary.

Table 2 Morphological characteristics of the 30 patients

Conventional cytogenetics

Blood and bone marrow cells were collected at diagnosis, cultured for 24 and/or 48 h, and synchronized with fluorodeoxyuridine17 in most cases. (RHG) reverse heat Giemsa and/or (GTG) G-banding with trypsin-Giemsa banding techniques were used, depending on the centre. Karyotype was established according to the International System for Human Cytogenetic Nomenclature 2005.18 All karyotypes were collegially reviewed by members of the GFCH. Fluorescence in situ hybridization (FISH) and molecular analyses were done on the retained cases (Table 3).

Table 3 Karyotype of the 30 cases, FISH results and type of fusion transcripts in the 22 patients tested by RT-PCR

Fluorescence in situ hybridization

Fluorescence in situ hybridization was done on the cytogenetic pellets in all cases except 16 and 17, for which material was not available. Except for case 8, all analyses were done in one centre (Strasbourg). Probes used for chromosome band 8p11 exploration (MYST3) were from telomere to centromere, bacterial artificial chromosome (BAC) RP11-313J18 and RP11-589C21 (only BAC RP11-313J18 for case 8), labelled with SpectrumRed (Vysis, Downers Grove, IL, USA). For chromosome 16 exploration, BAC RP11-619A23 at 16p13 (CREBBP) labelled with SpectrumGreen (Vysis) was used. In cases 27 and 29, BACs RP11-350N15 and RP11-513D5 were used to study FGFR1 (8p11). For EP300 exploration at 22q13, BACs RP11-12M9 (SpectrumRed), RP11-422A16 (SpectrumGreen) and RP1-85F18 (SpectrumGreen) were used (case 27). BACs were provided by the Sanger institute (Cambridge, UK). Multi-FISH was performed (Metasystems, Altlusheim, Germany) to characterize case 1 and 27 abnormalities.

Molecular analysis

RNA was obtained for 22 of the 30 patients. For patients 2, 9, 10, 14, 15, 22, 25 and 28, no material was available. Reverse transcription PCR (RT-PCR) analyses were done on RNA extracted by the Allprep DNA/RNA isolation kit (Qiagen, Hilden, Germany) from blood or bone marrow blast cells of patients and normal lymphocytes as negative control. The human NMA gene (locus ID: 25805) was used to control RT-PCR efficiency. Detection of MYST3-CREBBP and/or CREBBP-MYST3 fusion transcripts was done as described:14 an RT-PCR for the detection of types I, II and III, completed by the search for types IV and V if types I, II and III were absent. PCR products were visualized on 2% agarose gel with ethidium bromide. Primers are listed in Table 4.

Table 4 Primers used for RT-PCR

Detection of type I (MYST3 exon 16-CREBBP exon 3), II (MYST3 exon 16-CREBBP exon 4) and III (MYST3 exon 17-CREBBP exon 2 or exon 4) MYST3-CREBBP transcripts:19, 20 a nested PCR with primer combinations exon 16 MYST3_3536F/exon 5 CREBBP_1201R and exon 16 MYST3_3558F/exon 3 CREBBP_404R amplified an 330- or an 1215-bp fragment in type I and type III, respectively. PCR with primer combination exon 16 MYST3_3536F/exon 5 CREBBP_1201R amplified an 410-bp fragment in type II.

Detection of type IV (MYST3 exon 15-CREBBP exon 4) and V (MYST3 exon 15-CREBBP exon 5) MYST3-CREBBP transcripts:14 PCR with primer combination exon 15 MYST3_3319F/exon 5 CREBBP_1201R amplified an 350- or an 176-bp fragment in type IV and type V, respectively.

Detection of the reciprocal CREBBP-MYST3 transcripts:14, 20 the reciprocal CREBBP-MYST3 fusion transcripts for the different types were detected with nested PCR and primer combinations exon 2 CREBBP_96F/exon 17 MYST3_3953R and exon 2 CREBBP_174F/exon 17 MYST3_3844R.

Results and discussion

According to the Mitelman database,21 66 cases of t(8;16)(p11;p13) have been described in the literature. Although the largest series contained only five cases, our series includes 30 cases. The t(8;16)(p11;p13) was previously described in <1% in AML. Female patients represented 67% of our series (20/30 cases), in contrast with previous studies in which both sexes were equally represented.6 Children and young adults were a minority, with a mean age for both sexes of 59.4 years (range 15–82). One patient was 15 years old, nine patients were from 30 to 49 years old, 11 from 50 to 69 years old and nine more than 70 years old. Three cases of congenital AML with t(8;16)(p11;p13) have been described,22, 23 but none was included in our series.

Clinical features

At the time of AML diagnosis, nine patients had cutaneous localization (30%), five hepatomegaly, four splenomegaly, three adenopathy, three bone pains, one mucosa localization and one gingival hypertrophy. Cutaneous infiltrates are typical but not specific to this disorder as they are observed in AML-M4 or -M5 without t(8;16). Disseminated intravascular coagulation was present in 12 patients (40%).

Only seven AML from our series were de novo, and 23 patients (76.7%) had a previous history of solid tumour and/or haematological malignancy before the appearance of AML: 12 breast cancers, four chronic myelomonocytic leukaemias (CMMLs), three lymphomas, two AMLs, one acute lymphoid leukaemia, two testicle cancers and one prostate cancer (Table 1). Two patients (cases 6 and 19) had two malignant diseases during the previous years. The mean time between the primary disease and AML with 8p11 abnormality was approximately 25 months for the 17 cases for which the date of the primary disease was known. Among the 20 female patients, four had de novo AML and 12 had a history of breast cancer, representing 75% of t-AML in female subjects. Four patients, who presented CMML 13–24 months before the diagnosis of AML, have to be distinguished from other secondary cases as AML was an evolution of CMML. Two of them were myelomonocytic AML (M4). Monocytic AML is a common evolution for CMML, and we show that MYST3 abnormality can be observed in such cases.

Among the 66 cases of t(8;16) described in the literature,21 21 cases were therapy-related (32%), which represents a lower rate than in our series (77%). Among those 21 reported cases, 14 were secondary to solid cancers (eight breast cancers) and seven to haematological malignancies.

The t(8;16) may be associated with previous treatment with anthracyclines.24 In our study, 30% of the secondary cases had a previous anthracycline treatment (seven cases), 48% had alkylating agent (11 cases), 30% had topoisomerases II inhibitor (seven cases) and 57% had radiotherapy (13 cases). In three cases, therapeutic records were incomplete. Thus, we cannot confirm the association of t(8;16) with prior anthracycline therapy.

Haematological features

Peripheral blood examination showed mean haemoglobin level of 10.5 g per 100 ml (range 6.8–14.5), mean platelet count of 82 × 109/l (range 14–375) and mean white blood cell count of 24 × 109/l (range 1.5–112). Bone marrow aspiration was hypercellular in 16 cases, with a mean blast cell count of 68%. As expected, all acute leukaemias were monocytic. According to the FAB classification, 17 cases were AML-M5a, nine cases -M5b, two cases -M4 and one case -M5 unclassifiable because of the presence of necrosis (Table 2). No dysplasia was observed. Among the 28 bone marrow smears of good quality, the presence of cytoplasmic vacuoles, sometimes abundant, was noted in 21 cases (75%). Erythrophagocytosis was present in 21/28 cases (75%) and was major in eight cases. Cytoplasmic vacuoles and erythrophagocytosis were both observed in 18/28 cases. Among the nine cases analysed for esterase, eight had a strong activity and one case had low activity. Among the nine cases analysed for peroxidase, five had no peroxidase activity and four had a very strong activity, all AML-M5a. In 19 cases, cytochemical analyses were not available.

Immunophenotypic analysis was available for 25 patients (all except cases 2, 17, 25, 28 and 29) and showed negative CD34 in 21/23 (91%), positive CD4 in 18/19 (95%), positive CD14 in 11/20 (55%), positive CD56 in 13/18 (72%), positive CD33 in 24/25 (96%), positive CD13 in 17/24 (71%), positive CD15 in 18/19 (95%), positive HLA-DR in 19/21 (90%) and positive CD11b in 8/14 cases (57%) (data not shown). In a study of 54 cases of de novo monocytic AML,25 the same pattern of antigen expression was observed. The only difference was the expression of CD11b (normally expressed in myeloid and NK cells) in 100% of study by Xu25 but in only 57% of our cases; however, CD11b was explored here in only 14 cases, which is insufficient to draw any interpretation. In conclusion, monocytic leukaemias with or without t(8;16) do not differ by their antigen expression.

Cytogenetic features

Karyotypes are reported in Table 3. Sixteen cases (53.3%) showed simple karyotypes with isolated 8p11 translocation. Seven karyotypes (23.3%) showed the 8p11 translocation with a single additional abnormality: −Y, add(1)(p36), +i(5)(p10), +8, t(11;12)(p10;p10), ider(13)(q10)del(13)(q13q22) and del(20)(q12). Seven karyotypes (23.3%) were complex (three abnormalities or more). Partial or complete trisomy 8 was present in six cases (20%). Chromosome 7 abnormalities, often present in therapy-related disorders, were present in three cases, and chromosome 5 abnormality was present in one case. It has to be noted that for cases 8 and 24, the t(8;16) appeared as a secondary event. The primary abnormality was −Y or del(20)(q12). Those two cases were de novo AMLs.

Twenty-eight cases were analysed by FISH. FISH analysis failed to prove t(8;16) in case 15, despite the analysis of 80 metaphases. Two hybridization patterns were observed (Figure 1). Considering the position of the probes, this suggested a variation in the breakpoint in CREBBP, confirmed by molecular analysis (see Molecular features).

Figure 1

FISH analysis using BAC RP11-313J18 and BAC RP11-589C21 in 8p11, labelled in SpectrumRed, BAC RP11-619A23 in 16p13, labelled in SpectrumGreen. (a) Case 2, showing one red signal on normal chromosome 8, a second red signal on der(16)t(8;16), one green signal on normal chromosome 16 and one fused signal on der(8)t(8;16). Cases 3–5, 9–14, 18–23, 25 and 28 were similar (pattern 1). (b) Case 1, showing one fused signal on der(16)t(8;16) instead of one red signal. Cases 6, 7, 8, 24, 26 and 30 were similar (pattern 2). BAC, bacterial artificial chromosome; FISH, fluorescence in situ hybridization.

One variant translocation was identified (case 8) with a ‘classical’ der(8)t(8;16) with MYST3-CREBBP fusion transcript type V and a der(16)t(8;16)(p11;p13)ins(16;8)(p13;q2223q24.1). Some 8q material was present between CREBBP and MYST3 on the der(16). Consequently, FISH signals were not fused and the CREBBP-MYST3 transcript was absent. Two patients with a variant t(8;16) have been reported. The first one was a t(8;18;16)(p11;q21;p13)26 in a young boy with AML-M5b, and the second was an inv(8)(p11q24.3) with masked t(8;16)27 in a 60-year-old female patient with AML-M5.

Two alternative translocations were identified in our series, in which 22q13 and 19q13.3 were implicated instead of 16p13 (Table 3). FISH analysis suggested MYST3 involvement without CREBBP abnormality. FGFR1 involvement was excluded in both cases. The karyotype of patient 27 (AML-M5 preceded by CMML) was complex, with der(8)(8qter->8q?13228p11 → 8qter) and der(22)(22pter->22q138) identified by multicolor FISH. FISH analysis with specific BAC confirmed the involvement of the MYST3 and EP300 genes (data not shown). A t(8;22)(p11;q13) has been described in two cases,9, 28 fusing MYST3 to EP300.10 Both cases were AML-M5, de novo in the first one, from progression of a CMML in the second one. The breakpoint was in the same exon (exon 3) and involved codon 117, as in the t(8;16). Both fusion transcripts were expressed in the two cases. Adenoviral E1A-associated protein EP300 is a homologue of CREBBP and has acetyltransferase activity like CREBBP. The fusion protein plays an abnormal transcriptional co-activator role in AML. Patient 29 (de novo AML-M5a) had a simple karyotype with t(8;19)(p11;q13.3). Two such cases have been reported. The first one was a male patient with AML-M5a and additional abnormalities t(8;19),add(1)(q?),add(16)(q?).8 The second one was a young female patient with AML-M4 and a simple t(8;19).29 The gene in 19q13 is unknown. Neither inv(8)(p11q13) involving TIF2/NCOA2 (nuclear receptor coactivator 2), described in seven cases,11, 12, 30, 31, 32, 33 nor other recurrent alternative translocations—t(6;8)(q27;p11),34 t(8;14)(p11;q11.1),35 t(3;8;17)(q27;p11;q12),36 t(2;8)(p23;p11)37 and t(8;20)(p11;q13)38—were found in our series.

Molecular features

In 13 of 22 cases, a 330-bp fragment was amplified with the first set of primers, corresponding to a type I MYST3-CREBBP (Table 3). Cases 1, 6, 7, 8, 24, 26, 27, 29 and 30 were not amplified (Figure 2a). With the second set of primers, a 350-bp fragment was found in cases 1, 6, 7, 24, 26 and 30 corresponding to type IV MYST3-CREBBP, and an 176-bp fragment was found in cases 1 and 8 corresponding to type V MYST3-CREBBP. Case 1 presented with a strong band of 350 bp and a weak band of 176 bp (Figure 2b). The reciprocal CREBBP-MYST3 type I transcript was detected as a 229-bp fragment in 12/13 cases with type I transcript. In cases 7 and 26, a 1256-bp fragment was amplified corresponding to the reciprocal IV transcript. In case 30, the reciprocal transcript differed from the other type IV cases, with a band of 500 bp. In cases 1, 6, 8, 16 and 24, no reciprocal transcript was found (Figure 2c). Cases 27 and 29 were negative for all types of transcripts tested (data not shown). To date, 16 cases with t(8;16)(p11;p13) have been characterized by RT-PCR.5, 19, 20, 24, 39, 40, 41 Type I transcript is the most frequent fusion product (13 cases/16); breakpoints map in MYST3 intron 16. Type II was described in two cases associated with type I and MYST3 and CREBBP gene fusions result in an out-of-frame sequence and in a putative truncated protein.24 In rare cases (3/16), the breakpoint is in MYST3 exon 17, which is fused to CREBBP exon 2 or 45, 19, 20 defining type III. Recently, a fourth and fifth type have been described in two cases, in which the MYST3-CREBBP fusion has lost MYST3 exon 16, suggesting that the breakpoint occurs in intron 15.14 In our study, type I was the most frequent transcript (13/20 cases). The other cases were types IV (cases 1, 6, 7, 24, 26 and 30) and V (cases 1 and 8). Two of these rare cases have been previously described (cases 7 and 8).14 In some reports, the reciprocal CREBBP-MYST3 transcript was not amplified19, 40 or was out-of-frame.5 Therefore, MYST3-CREBBP, and not CREBBP-MYST3 transcript, is believed to be of importance in the leukaemogenesis process.19 We did not find a reciprocal transcript for five patients. Patient 1 showed both type IV and type V MYST3-CREBBP transcripts. Although no quantitative RT-PCR was performed, it was evident from the intensity of the amplified fragments that type IV was the most abundant transcript in this sample. Panagopoulos et al.24 described two patients with both type I and type II CREBBP-MYST3 transcripts. In patient 30, the 500-bp fragment corresponding to the reciprocal transcript was unusual, probably because of different breakpoints in MYST3 and/or CREBBP genes. No difference in type was observed between de novo (three type I, one type IV, one type V and one alternative translocation) or therapy-related 8p11 AML.

Figure 2

Nested PCR and partial sequences of MYST3-CREBBP and CREBBP-MYST3 fusions. (a) The first set of primer combinations allowed the detection of type I MYST3-CREBBP fusion transcript. Thirteen out of 20 cases showed a 330-bp fragment, corresponding to type I. Cases 1, 6, 7, 8, 24, 26 and 30 were not amplified. (b) The second set of primer combination allowed the detection of types IV and V MYST3-CREBBP fusion transcripts. Cases 6, 7, 24, 26 and 30 were positive for type IV. Case 8 was positive for type V. Case 1 was positive for both types IV and V. (c) The reciprocal transcript CREBBP-MYST3 fusion transcript was observed in 15/20 cases. Twelve out of 20 cases were type I. Cases 7 and 26 were type IV. Case 30 showed an unusual 500-bp band. Cases 1, 6, 8, 16 and 24 were not amplified. N: normal lymphocytes; G: genomic DNA; M: 100-bp DNA molecular weight ladder. CREBBP, CREB-binding protein; MYST3, MYST histone acetyltransferase 3.

There was a relation between the hybridization pattern observed by FISH analysis and the type of fusion transcript. Cases 2, 3–5, 9–14, 18–23, 25 and 28 showed no split signal of the CREBBP probe (all the probe moved on der(8)t(8;16)) (pattern 1) and type I fusion transcript. Cases 1, 6, 7, 8, 24, 26 and 30 showed one split signal of this probe (pattern 2) and type IV and/or V fusion transcript, as the 16p13 breakpoint was more telomeric in those cases. Variation of MYST3 breakpoint was not visible by FISH, with the selected probes.

Prognostic features

Eight patients (27%) of this study were in remission at the time of collection of the data (5 months to 4 years after the diagnosis) (Table 1). Two patients relapsed 17 months and 3–4 months after diagnosis. No remission was achieved for patient 22 with a recession of 1.5 months. Half of the patients deceased during the first 10 months after diagnosis: four during the first week after diagnosis, six between 1 week and 3 months and five between 3 and 10 months. Four patients were lost to follow-up rapidly after diagnosis (3 months maximum). The t(8;16)(p11;p13) has been described in two cases with complete spontaneous remission, during acute monoblastic leukaemia42 and congenital myelosarcoma.43 A t(8;16)(q11;p13), probably involving CREBBP, has also been reported in a congenital AML-M4 with spontaneous regression.44 In contrast to these three regressive cases, the prognosis of AML with t(8;16) is overall poor. Indeed, although patients of our series were often old and therapies were different, our data confirm the poor prognosis of MYST3-linked AML.


We have reported a series of 30 AML with MYST3 abnormality. Patients were mostly women and the mean age was 60 years. The majority of cases were secondary AML to solid cancer, haematological malignancy or both. Disseminated intravascular coagulation was present in 40% of cases. AMLs were monocytic (rarely myelomonocytic), with erythrophagocytosis and cytoplasmic vacuoles. Immunophenotype showed negative CD34 and positive CD56 as generally found in monocytic leukaemia. Twenty-eight cases were t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case showed a variant of the t(8;22)(p11;q13) and one case showed a t(8;19)(p11;q13), suggesting that t(8;16)(p11;p13) is the main translocation and that other abnormalities are variant, complex or alternative translocations. Molecular study showed that type I was the most frequent MYST3-CREBBP fusion transcript. MYST3 abnormality was associated with poor prognosis. All these features suggest that AML with MYST3 abnormality is a specific entity that might be individualized in the World Health Organization classification. Subsequent studies are necessary to identify new translocations involving MYST3 and new partner genes (such as the one in 19q13) and to explain the involvement of the abnormal MYST3 protein in leukaemogenesis.


  1. 1

    Heim S, Avanzi GC, Billstrom R, Kristoffersson U, Mandahl N, Bekassy AN et al. A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia. Br J Haematol 1987; 66: 323–326.

    CAS  Article  Google Scholar 

  2. 2

    Lai JL, Zandecki M, Jouet JP, Savary JB, Lambiliotte A, Bauters F et al. Three cases of translocation (8;16)(p11;p13) observed in acute myelomonocytic leukemia: a new specific subgroup? Cancer Genet Cytogenet 1987; 27: 101–109.

    CAS  Article  Google Scholar 

  3. 3

    Huret J, Pérot C . t(8;16)(p11;p13). In: Atlas Genet Cytogenet Oncol Haematol 1998. URL:

  4. 4

    Vizmanos JL, Larrayoz MJ, Vazquez I, Odero MD, Hernandez R, Lahortiga I et al. Remission of acute monocytic leukemia, secondary to treatment with epipodophyllotoxins, in a patient with t(8;16)(p11;p13) and MYST3-CREBBP fusion. Cancer Genet Cytogenet 2004; 152: 177–178.

    CAS  Article  Google Scholar 

  5. 5

    Borrow J, Stanton Jr VP, Andresen JM, Becher R, Behm FG, Chaganti RS et al. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 1996; 14: 33–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Huret J, Senon S . MYST3 (MYST histone acetyltransferase (monocytic leukemia) 3. In: Atlas Genet Cytogenet Oncol Haematol 2005. URL:

  7. 7

    Huret J . CREBBP (CREB binding protein (Rubinstein-Taybi syndrome)). In: Atlas Genet Cytogenet Oncol Haematol 2000. URL:

  8. 8

    Tanzer J, Brizard A, Guilhot F, Benz-Lemoine E, Dreyfus B, Lessard M et al. [Acute leukemia with translocation (8;16)]. Nouv Rev Fr Hematol 1988; 30: 83–87.

    CAS  PubMed  Google Scholar 

  9. 9

    Lai JL, Zandecki M, Fenaux P, Preudhomme C, Facon T, Deminatti M . Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13). Cancer Genet Cytogenet 1992; 60: 180–182.

    CAS  Article  Google Scholar 

  10. 10

    Chaffanet M, Gressin L, Preudhomme C, Soenen-Cornu V, Birnbaum D, Pebusque MJ . MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). Genes Chromosomes Cancer 2000; 28: 138–144.

    CAS  Article  Google Scholar 

  11. 11

    Coulthard S, Chase A, Orchard K, Watmore A, Vora A, Goldman JM et al. Two cases of inv(8)(p11q13) in AML with erythrophagocytosis: a new cytogenetic variant. Br J Haematol 1998; 100: 561–563.

    CAS  Article  Google Scholar 

  12. 12

    Liang J, Prouty L, Williams BJ, Dayton MA, Blanchard KL . Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2. Blood 1998; 92: 2118–2122.

    CAS  Google Scholar 

  13. 13

    Esteyries S, Perot C, Adelaide J, Imbert M, Lagarde A, Pautas C et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia 2008; 22: 663–665.

    CAS  Article  Google Scholar 

  14. 14

    Murati A, Adelaide J, Quilichini B, Remy V, Sainty D, Stoppa AM et al. New types of MYST3-CBP and CBP-MYST3 fusion transcripts in t(8;16)(p11;p13) acute myeloid leukemias. Haematologica 2007; 92: 262–263.

    CAS  Article  Google Scholar 

  15. 15

    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the acute leukaemias. French–American–British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.

    CAS  Article  Google Scholar 

  16. 16

    Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press Lyon, 2001.

    Google Scholar 

  17. 17

    Weber L, Garson O . Fluorodeoxyuridine synchronization of bone marrow cultures. Cancer Genet Cytogenet 1983; 8: 123–132.

    Article  Google Scholar 

  18. 18

    Lisa G, Shaffer NT . ISCN 2005, An International System for Human Cytogenetic Nomenclature. Karger 2005.

  19. 19

    Panagopoulos I, Fioretos T, Isaksson M, Mitelman F, Johansson B, Theorin N et al. RT-PCR analysis of acute myeloid leukemia with t(8;16)(p11;p13): identification of a novel MOZ/CBP transcript and absence of CBP/MOZ expression. Genes Chromosomes Cancer 2002; 35: 372–374.

    CAS  Article  Google Scholar 

  20. 20

    Schmidt HH, Strehl S, Thaler D, Strunk D, Sill H, Linkesch W et al. RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications. Leukemia 2004; 18: 1115–1121.

    CAS  Article  Google Scholar 

  21. 21

    Mitelman F, Johansson B, Mertens F (eds). Mitelman Database of Chromosome Aberrations in Cancer. Available at Accessed on 16 July 2007.

  22. 22

    Bernstein R, Pinto MR, Spector I, Macdougall LG . A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia. Cancer Genet Cytogenet 1987; 24: 213–220.

    CAS  Article  Google Scholar 

  23. 23

    Hanada T, Ono I, Minosaki Y, Moriyama N, Nakahara S, Ohtsu A . Translocation t(8;16)(p11;p13) in neonatal acute monocytic leukaemia. Eur J Pediatr 1991; 150: 323–324.

    CAS  Article  Google Scholar 

  24. 24

    Panagopoulos I, Isaksson M, Lindvall C, Bjorkholm M, Ahlgren T, Fioretos T et al. RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13). Genes Chromosomes Cancer 2000; 28: 415–424.

    CAS  Article  Google Scholar 

  25. 25

    Xu Y, McKenna RW, Wilson KS, Karandikar NJ, Schultz RA, Kroft SH . Immunophenotypic identification of acute myeloid leukemia with monocytic differentiation. Leukemia 2006; 20: 1321–1324.

    CAS  Article  Google Scholar 

  26. 26

    Mo J, Lampkin B, Perentesis J, Poole L, Bao L . Translocation (8;18;16)(p11;q21;p13). A new variant of t(8;16)(p11;p13) in acute monoblastic leukemia: case report and review of the literature. Cancer Genet Cytogenet 2006; 165: 75–78.

    CAS  Article  Google Scholar 

  27. 27

    Chaffanet M, Mozziconacci MJ, Fernandez F, Sainty D, Lafage-Pochitaloff M, Birnbaum D et al. A case of inv(8)(p11q24) associated with acute myeloid leukemia involves the MOZ and CBP genes in a masked t(8;16). Genes Chromosomes Cancer 1999; 26: 161–165.

    CAS  Article  Google Scholar 

  28. 28

    Soenen V, Chaffanet M, Preudhomme C, Dib A, Lai JL, Fletcher JA et al. Identification of a YAC spanning the translocation breakpoint t(8;22) associated with acute monocytic leukemia. Genes Chromosomes Cancer 1996; 15: 191–194.

    CAS  Article  Google Scholar 

  29. 29

    Stark B, Resnitzky P, Jeison M, Luria D, Blau O, Avigad S et al. A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8:16)(p11:p13), in a patient with the variant t(8:19)(p11:q13)—case report and review of the literature. Leuk Res 1995; 19: 367–379.

    CAS  Article  Google Scholar 

  30. 30

    Billio A, Steer EJ, Pianezze G, Svaldi M, Casin M, Amato B et al. A further case of acute myeloid leukaemia with inv(8)(p11q13) and MOZ-TIF2 fusion. Haematologica 2002; 87: ECR15.

    PubMed  Google Scholar 

  31. 31

    Murati A, Adelaide J, Popovici C, Mozziconacci MJ, Arnoulet C, Lafage-Pochitaloff M et al. A further case of acute myelomonocytic leukemia with inv(8) chromosomal rearrangement and MOZ-NCOA2 gene fusion. Int J Mol Med 2003; 12: 423–428.

    CAS  PubMed  Google Scholar 

  32. 32

    Panagopoulos I, Teixeira MR, Micci F, Hammerstrom J, Isaksson M, Johansson B et al. Acute myeloid leukemia with inv(8)(p11q13). Leuk Lymphoma 2000; 39: 651–656.

    CAS  Article  Google Scholar 

  33. 33

    Strehl S, Konig M, Mann G, Haas OA . Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia. Blood 2001; 97: 805–808.

    CAS  Article  Google Scholar 

  34. 34

    Brizard A, Guilhot F, Huret JL, Benz-Lemoine E, Tanzer J . The 8p11 anomaly in ‘monoblastic’ leukaemia. Leuk Res 1988; 12: 693–697.

    CAS  Article  Google Scholar 

  35. 35

    Slovak ML, Nemana L, Traweek ST, Stroh JA . Acute monoblastic leukemia (FAB-M5b) with t(8;14)(p11;q11.1). Cancer Genet Cytogenet 1991; 56: 237–242.

    CAS  Article  Google Scholar 

  36. 36

    Bertheas MF, Jaubert J, Vasselon C, Reynaud J, Pomier G, Le Petit JC et al. A complex t(3;8;17) involving breakpoint 8p11 in a case of M5 acute nonlymphocytic leukemia with erythrophagocytosis. Cancer Genet Cytogenet 1989; 42: 67–73.

    CAS  Article  Google Scholar 

  37. 37

    Imamura T, Kakazu N, Hibi S, Morimoto A, Fukushima Y, Ijuin I et al. Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11). Genes Chromosomes Cancer 2003; 36: 413–419.

    CAS  Article  Google Scholar 

  38. 38

    Esteyries S, Perot C, Adelaide J, Imbert M, Lagarde A, Pautas C et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia 2007; 22: 663–665.

    Article  Google Scholar 

  39. 39

    Panagopoulos I, Isaksson M, Lindvall C, Hagemeijer A, Mitelman F, Johansson B . Genomic characterization of MOZ/CBP and CBP/MOZ chimeras in acute myeloid leukemia suggests the involvement of a damage-repair mechanism in the origin of the t(8;16)(p11;p13). Genes Chromosomes Cancer 2003; 36: 90–98.

    CAS  Article  Google Scholar 

  40. 40

    Rozman M, Camos M, Colomer D, Villamor N, Esteve J, Costa D et al. Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes Chromosomes Cancer 2004; 40: 140–145.

    CAS  Article  Google Scholar 

  41. 41

    Tasaka T, Matsuhashi Y, Uehara E, Tamura T, Kakazu N, Abe T et al. Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): case report and review of the literature. Leuk Lymphoma 2004; 45: 621–625.

    Article  Google Scholar 

  42. 42

    Sainati L, Bolcato S, Cocito MG, Zanesco L, Basso G, Montaldi A et al. Transient acute monoblastic leukemia with reciprocal (8;16)(p11;p13) translocation. Pediatr Hematol Oncol 1996; 13: 151–157.

    CAS  Article  Google Scholar 

  43. 43

    Classen CF, Behnisch W, Reinhardt D, Koenig M, Moller P, Debatin KM . Spontaneous complete and sustained remission of a rearrangement CBP (16p13)-positive disseminated congenital myelosarcoma. Ann Hematol 2005; 84: 274–275.

    Article  Google Scholar 

  44. 44

    Weintraub M, Kaplinsky C, Amariglio N, Rosner E, Brok-Simoni F, Rechavi G . Spontaneous regression of congenital leukaemia with an 8;16 translocation. Br J Haematol 2000; 111: 641–643.

    CAS  Article  Google Scholar 

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We thank cytologists and the members of the Groupe Français d'Hématologie Cellulaire: Jean-Philippe VIAL, Estelle GUERIN, Marguerite MICHEAU (Bordeaux), Danielle TREILLE-RITOUET (Lyon Sud), Marie-Paule CALLAT, Gérard BUCHONNET (Rouen), Bernardine FAVRE-AUDRY, Marc MAYNADIE (Dijon), Bruno VERHASSELT, Jan PHILIPPE, Lucien NOENS (Gent), Richard GARAND (Nantes), Christine ARNOULET (Marseille), Franck GENEVIEVE, Jacques GARDAIS (Angers), Jean-François CLAISSE (Amiens), André PETIT, Claire LESPANEL (Tours), Sylvie DALIPHARD (Reims), Christian VASSELON (Saint Etienne), Catherine SETTEGRANA (Pitié-Salpêtrière, Paris).

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Correspondence to C Gervais or M-J Mozziconacci.



Participant centres (number of patients of each centre is indicated in parentheses): CHU d'Angers (1); CHU de Bordeaux (4); CHU de Dijon (2); Centre de Génétique de Gent (2); Hôpital de Lieges (1*); CHU de Lyon-Sud (3); Institut Paoli-Calmettes, Marseille (2); CHU de Nantes (2); CHU de Reims (1); CHU de Rouen (3); CHU de Tours (1); Paris, Hôpital Pitié-Salpêtrière (1); Paris, Hôpital Saint-Antoine (2); Paris, Hôpital Saint-Louis (2*); CHU de Saint-Etienne (1); CHU de Strasbourg (5). *Cases not included in the series (absence of cytological review).

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Gervais, C., Murati, A., Helias, C. et al. Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogénétique hématologique. Leukemia 22, 1567–1575 (2008).

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  • AML
  • MYST3
  • t(8;16)(p11;p13)

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