Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML


t(8;21)(q22;q22) is the most frequently observed karyotypic abnormality associated with acute myeloid leukemia (AML), especially in FAB M2. Clinically, this type of AML often shows eosinophilia and has a high complete remission rate with conventional chemotherapy. t(8;21) AML is also frequently associated with additional karyotypic aberrations, such as a loss of the sex chromosome; however, it is unclear whether these aberrations change the biological and clinical characteristics of t(8;21) AML. To investigate this issue, 94 patients with t(8;21) AML were categorized according to their additional karyotypic aberrations, which were detected in more than three cases, and then morphologic features, phenotypes, expression of cytokine receptors, and clinical features were compared to t(8;21) AML without other additional aberrant karyotypes. t(8;21) AML with loss of the sex chromosome and abnormality of chromosome 9 were found in 27 cases (29.3%) and 10 cases (10.6%), respectively; however, no differences were observed from the t(8;21) AML without other additional karyotypes in terms of morphological and phenotypic features. There was also no significant difference in the clinical outcome among these three groups. On the other hand, trisomy 4 was found in three cases (3.2%) and these cells showed low expressions of CD19 (P=0.06) and IL-7 receptor (P=0.05), and high expressions of CD33 (P=0.13), CD18 (P=0.03), and CD56 (P=0.03) when compared to t(8;21) AML without additional karyotypes. Moreover, all three t(8;21) AML cases with trisomy 4 did not show eosinophilia in their bone marrow and died within 2.4 years. These observations suggest that additional karyotypic aberration, t(8;21) with trisomy 4 is rare, but it may constitute a distinctive subtype of t(8;21) AML.


Acute leukemia with a particular chromosomal abnormality often shows unique biological and clinical characteristics. In these cases, the translocation (8;21)(q22;q22) (t(8;21)) is one of the most common karyotypic abnormalities in acute myeloid leukemia (AML) and is closely associated with the AML-M2 subtype (French–American–British Classification; FAB1,2) (18–40%).3 This type of AML has a high complete remission (CR) rate with standard chemotherapy, and a prolonged survival when sequential high-dose cytarabine is administered.4,5,6,7 Previous reports including ours have demonstrated that t(8;21)AML shows high levels of CD34 and DR expression, with a prevalent positivity for CD19 and CD56 surface markers and a low expression of CD33 and CD7 when compared to AML with normal or other aberrant karyotypes, and eosinophilia is also often observed in t(8;21) AML.8,9,10,11,12,13,14,15 Cytogenetically, the t(8;21) AML is frequently associated with a loss of the sex chromosome Y in males and inactive X in females;3 3.4% of the cases are variant translocations.16 However, the influence of these variant translocations or additional chromosomal abnormalities on the characteristics of t(8;21) AML is still unclear.

To investigate whether additional chromosomal abnormalities may change the biological and clinical characteristics of t(8;21) AML, a large number of patients with t(8;21) AML (94 cases) were categorized into subgroups according to their additional karyotypic aberrations and then morphological features, phenotypes, expression of cytokine receptors, and clinical features in these groups were analyzed.

Materials and methods

Patient selection

From 1987 to 2001, 94 Japanese adult patients (age 15 years or older) newly diagnosed with t(8;21) AML were consecutively registered from seven collaborating hospitals after obtaining informed consent. All patients have been prospectively enrolled in 1 of the 5 Japan multicenter trials. Induction therapies were as follows: JALSG-AML87, behenoyl cytarabine (BHAC) or cytarabine (Ara-C) plus daunomycin (DNR) and 6-mercaptopurine (6MP);17,18 JALSG-AML92, BHAC, DNR, and 6MP with or without etoposide (ETP);19 JALSG-AML95, Ara-C, and DNR;20 JALSG-AML97, Ara-C, and idarubicin hydrochloride (IDR);21,22 B-DOMP, DNR, VCR, BHAC, 6-MP, PDN with or without ETP. High- or intermediate-dose Ara-C as postremission therapy was not used on any patients. CR was defined as the presence of less than 5% blast cells in bone marrow (BM) aspirate after induction therapy.

Flow cytometric analysis of surface antigens

Leukemic BM or peripheral blood (PB) samples were collected. Mononuclear cells (MNC) were separated by Ficoll–Hypaque density gradient centrifugation. In all cases, over 90% of the isolated cells had leukemic cell-like morphology. Immunostaining for leukemic cells was carried out as described previously.23 CD19, CD20 (Becton Dickinson Immunocytometry Systems, San Jose, CA, USA) and CD10 (DAKO, Glostrup, Denmark) were used as B-cell markers. CD7, CD56, CD18, and CD25, all from Becton Dickinson Immunocytometry Systems, were used as T- or NK-cell markers. CD14, CD11b, CD11c, CD33, CD34, CD38 (Becton Dickinson Immunocytometry Systems), and CD13 (CALTAG Laboratories, Burlingame, CA, USA) were used as myeloid- or stem-cell markers. Flow cytometric analysis of cytokine receptors was performed using the following antibodies; mouse monoclonal antibodies against human IL-3 receptor α chain (IL-3Rα), c-kit, and granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) were purchased from PharMingen (San Diego, CA, USA). Mouse monoclonal antibodies against human IL-5Rα and IL-7Rα were obtained from Immunotech (Marseille, France), mouse monoclonal antibody against human granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor α chain (GM-CSFRα) was purchased from Genzyme (Cambridge, MA, USA). The expression of cytoplasmic Bcl-2 (DAKO) in leukemic cells was studied as described previously.13 For evaluation of the intensity of the cytokine receptors and Bcl-2 expressions, the assessment was performed by relative fluorescence intensity (RFI); RFI is the mean number of fluorescence intensity (FI) in log scale of monoclonal antibody-added sample – the mean number of FI in log scale of the isotype control.13

Cytogenetic analysis and interphase fluorescence in situ hybridization (FISH) of chromosome 4

A chromosomal analysis (G-banding) was performed as diagnosis on a 24 h in vitro BM cell culture. Interphase FISH of the chromosome 4 study was performed as previously reported.24 The cells of BM MNC from three cases of t(8;21) AML with trisomy 4 were transferred to multicompartmentalized microscope slides (DAKO) and dried by evaporation. The slides were dehydrated in ascending concentrations of alcohol, denatured, and dehydrated again. The cells were then probed using a mixture of chromosome 4 labeled with Spectrum Orange (Vysis, Downers Grove, IL, USA) and stained with DAPI (Vysis). At least 300 cells were observed in each sample.

Detection of AML1/ETO fusion gene by reverse transcriptase-polymerase chain reaction (RT-PCR)

RNA was extracted from primary leukemic cells and the expression of AML1/ETO gene was studied using RT-PCR, as described previously.25 PCR was performed for 35 cycles, under the following conditions: 1 min at 94°C for denaturating, 1 min at 57°C for annealing, and 2 min at 72°C for extending. The following oligonucleotide primers were used:26 sense, 5′-IndexTermAGC CAT GAA GAA CCA GG-3′; antisense, 5′-IndexTermAGG CTG TAG GAG AAT GG-3′; β-actin sense, 5′-IndexTermGTG GGG CGC CCC AGG CAC CA-3′; β-actin antisense, 5′-IndexTermGTC CTT AAT GTC ACG CAC GAT TTC-3′. The PCR products were electrophoresed on a 3% agarose gel, in comparison with the molecular-weight ladder (174 digested by Hae III) and stained with ethidium bromide for viewing under UV illumination.

Statistical analysis

The differences between single antigen expressions were evaluated by the Student's t-test using StatView software (SAS Institute, Cary, NC, USA). Patient survival data were analyzed by the Kaplan–Meier method and were compared by means of the log-rank test. Survival was calculated from the first day of induction therapy to death. Patients who underwent bone marrow transplantation (BMT) were censored at the date of BMT.


t(8;21) AML samples and classification by additional chromosomal abnormality

The aim of this study was to investigate whether additional chromosomal abnormality altered the characteristics and clinical features of t(8;21) AML. To investigate this issue, 94 AML cases with t(8;21) were categorized into five groups as follows; Group I (GI, 45 cases) without other karyotypic abnormalities, Group II (GII, 27 cases) with deletion of the sex chromosome, Group III (GIII, three cases) with trisomy 4, Group IV (GIV, 10 cases) with abnormal chromosome 9, and Group V (GV, nine cases) with other chromosomal abnormalities (Tables 1 and 2). The median ages were 49 (range 15–73), 47 (range 16–80), 48 (range 42–62), 45 (range 16–56), and 39 (range 17–63) years in patients of the GI, GII, GIII, GIV, and GV groups, respectively (Table 1).

Table 1 Distribution of patients with t(8;21) according to the FAB classification
Table 2 Karyotypic data, eosinophils in BM, and chemotherapy response of the patients in GIII, GIV, and GV

Morphologic features in t(8;21) AML

According to the FAB classification, five patients were M1, 88 M2, and one M4 (Table 1). As described previously,27,28 patients with t(8;21) AML typically present with FAB M2 morphology, with a minority of cases presenting M1 or M4. Although eosinophilia is one of the characteristics in morphological features of t(8;21) AML,11,15,27,29 BM smears from three cases of t(8;21) AML with trisomy 4 did not show any eosinophils (Tables 1 and 2 and Figure 1). Andrieu et al showed a well-defined scoring system, called the weighted score (WS), based on the attribution of different weights to define morphological parameters of t(8;21) AML.12 Using their system, leukemic cells of t(8;21) AML with trisomy 4 were scored, and all three cases had morphological features suggestive of a t(8;21) AML except eosinophilia (Table 3 and Figure 1).

Figure 1

Morphological features of t(8;21) AML. Leukemic cells of BM from t(8;21) AML patients were stained with May–Grunwald–Giemsa. (a) t(8;21) AML without another additional karyotype (Cases GI-15) shows a typical morphological abnormality. Eosinophilia was found in M2 case of GI-15 (a) but not in M1 case of GIII-1 (b) and M2 case of GIII-3.

Table 3 Application of the WS scores to t(8;21) AML with trisomy 4

Expression of surface antigens on t(8;21) AML

Table 4 and Figure 2 show the median percentage of positive cells, and the range and results of statistical analysis performed by the t-test are illustrated for each antigen. When additional chromosomal abnormality with t(8;21) AML groups (GII, GIII, GIV, and GV) was compared to t(8;21) AML without another aberrant karyotype (GI), differences were found for CD19, CD33, CD18, and CD56 expression on AML cells in GIII. The AML group with trisomy 4 (GIII) showed less expression of CD19 (median 6.3 vs 34.9%, P=0.06). In contrast, CD33 (68.0 vs 27.4%, P=0.13), CD18 (81.5 vs 48.0%, P=0.03), and CD56 (91.0% vs 44.0%, P=0.03) expressions were elevated in GIII patients. In the cytokine receptor expression on t(8;21) AML, IL-7Rα (38.6 vs 65.9, P=0.05) was expressed less on the cells in GIII (Table 5 and Figure 2).

Table 4 Median percentage of positive cells in patients with t(8;21)
Figure 2

Surface marker and cytokine receptor expressions on t(8;21) AML samples. Distributions of the CD19, c-kit, and IL-7R expressions on t(8;21) AML cells with trisomy 4 samples (GIII) were lower than those in the other types of t(8;21) AML (GI, GII, GIV, and GV). In contrast, CD18, CD33, and CD56 in G III were expressed higher than in other groups of t(8;21) AML. GI, Group I; GII, Group II; GIII, Group III; GIV, Group IV; GV, Group V. RFI, relative fluorescence intensity (see Materials and methods).

Table 5 Median relative fluorescence intensity (RFI) of cells in patients with t(8;21)

Previous investigations have shown that blasts from AML M2 with t(8;21) display high levels of CD34, and lower CD33 expression, with frequent positivity for CD19 and CD56 surface markers, and an absence of CD7 antigen expression when compared to t(8;21) negative M2 AML.9,12,30 In this study, we demonstrated that t(8;21) AML with trisomy 4 has lower expressions of CD19 and IL-7Rα, and displays higher CD33, CD18, and CD56 expressions.

Clinical features of t(8;21) AML

Clinically, the t(8;21) AML present at diagnosis in 7% of cases of adult de novo AML is generally associated with a high CR rate and prolonged disease-free survival.4,5,6 In our study, the CR rate of t(8;21) AML patients treated with conventional induction therapy was 95.3% and the 5-year survival rate was 52.0% (Table 1 and Figure 3a). Among the subgroups of t(8;21) AML patients, the overall survival was significantly shorter in patients whose cells had trisomy 4 (P<0.05) (Figure 3b).

Figure 3

Kaplan–Meier survival curves of patients with t(8;21) AML. All t(8;21) AML cases who received conventional induction chemotherapy were analyzed (total 85 cases; 40 cases in GI, 26 cases in GII, three cases in GIII, eight cases in GIV, and eight cases in GV). (a) The 5-year survival rate was 52.0% and median survival was 2.34 years. (b) Overall survival curves of patients with or without additional chromosomal abnormality. Median survival in each group is 2.34, 2.91, 0.88, 3.23, and 2.85 years in patients of the GI, GII, GIII, GIV, and GV groups, respectively. t(8;21) AML with trisomy 4 (GIII) showed significantly worse survival than other t(8;21) AML (vs GI, P=0.042; vs GII, P=0.030; vs GIV; P=0.021; vs GV; P=0.049). There were no differences among the survival curves of GI, GII, GIV, and GV; n, number of patients studied.

FISH analysis of chromosome 4

Analysis by interphase FISH using chromosome 4 probe also confirmed that three fluorescent signals were detected in 68, 75, and 80% of BM blastic cells in patients of the GIII-1, GIII-2, and GIII-3, respectively (Figure 4a). Two of those three patients (Cases GIII-2 and GIII-3) were CR after conventional induction chemotherapy and trisomy 4 was not detected in their BM samples using interphase FISH and karyotype analysis (Figure 4b). We could not prove whether erythroid cells were affected by trisomy 4 at the onset, because erythroid cells were less than 5% in their BM samples.

Figure 4

FISH analysis of chromosome 4 on t(8;21) AML with trisomy 4. Inter phase FISH analysis using a chromosome 4 probe was performed in BM cells from three cases of t(8;21) AML with trisomy (GIII). (a) Three hybridization signals in the nuclei were detected in 68% of the BM cells at diagnosis (Case GIII-1). (b) The cells with three signals were not detected in BM cells from Case GIII-3 after CR (less than 3%). At least 300 cells were observed in each sample.

Detection of the AML1/ETO gene on the cells with trisomy 4

The fusion gene of AML1 and ETO is causally related to the occurrence of t(8;21) AML.31,32 On the other hand, it has also been reported that some cases with t(8;21) lack the AML1/ETO fusion gene.33 Therefore, the expression of the AML1/ETO fusion gene was studied in the leukemic cells of t(8;21) AML with trisomy 4 (Cases GIII-1, GIII-2, and GIII-3) and was detected in all three samples (Figure 5). The expression of AML1/ETO fusion gene was also confirmed in other samples of t(8;21) AML with or without additional chromosomal abnormalities (data not shown). Kasumi-1,34 a cell line derived from an AML (M2) patient with t(8;21), was used as a positive control.

Figure 5

Expression of the AML1/ETO fusion gene in t(8;21) AML with trisomy 4 cases. Expression of the AML1/ETO fusion gene was detected in the cells from all three t(8;21) AML with trisomy 4 using RT-PCR analysis. Kasumi-1 was used as a positive control.


In this study, we show that t(8;21) AML with trisomy 4 is very rare since it was found in only three out of 94 cases (3.2%); however, the relevant clinical features of these cases are different from t(8;21) AML. Trisomy 4 as the sole karyotype aberration is an uncommon numerical chromosomal aberration in AML, the majority of cases being diagnosed as FAB M2 or M4.35,36,37 In the cytogenetic analysis of 305 patients with primary AML, two patients with trisomy 4 as the sole karyotype aberration were found (0.6%) and these two cases had a poor prognosis.36 Weber et al summarized 20 AML patients with trisomy 4. According to their study, the CR rate was 61%.36 Keung et al38 also reviewed the literature of acute leukemia with trisomy 4. The mean age was 47.8 years and there were 37 cases of AML, 27 (73%) cases were either M2 or M4 subtypes, three acute lymphoblastic leukemia, one undifferentiated leukemia, one biphenotypic leukemia, and three cases with myelodysplastic syndrome. Of the 28 cases of AML who were treated with induction chemotherapy, the CR rate was 72% and the median survival was 12 months. These observations including our results show that the clinical features of t(8;21) AML with trisomy 4 may be similar to those observed by other authors in patients with AML and trisomy 4 as an isolated change. It has been reported that CD56 expression in t(8;21) AML is associated with a significantly shorter CR duration and survival, and also found to be associated with extramedullary disease.14,39 All three t(8;21) AML with trisomy 4 expressed CD56 and had a poor prognosis; however, extramedullary disease was not found in these cases. Therefore, we cannot explain the relation between CD56 expression and trisomy 4, and further investigation will be necessary. While the development of AML with trisomy 4 secondary to chemo- or radiotherapy has also been suggested,36,40,41,42 our present three cases with trisomy 4 had no history of long-term medication, radiotherapy, or occupational exposure to any toxins.

In conclusion, our data suggest that morphological features, phenotypic findings, and clinical features of t(8;21) AML with trisomy 4 are different from those of t(8;21) AML. Even though trisomy 4 is likely to be a secondary event after the t(8;21) translocation, the presence of this additional numerical aberration may define a distinctive subtype of AML with t(8;21)/AML1/ETO fusion.


  1. 1

    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French–American–British Cooperative Group. Ann Intern Med 1985; 103: 620–625.

  2. 2

    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-M0). Br J Haematol 1991; 78: 325–329.

  3. 3

    Rowley JD . Recurring chromosome abnormalitoes in leukemia and lymphoma. Semin Hematol 1990; 27: 122–136.

  4. 4

    Fenaux P, Preudhomme C, Laï JL, Morel P, Beuscart R, Bauters F . Cytogenetics and their prognostic value in de novo acute myeloid leukaemia: a report on 283 cases. Br J Haematol 1989; 73: 61–67.

  5. 5

    Schiffer CA, Lee EJ, Tomiyasu T, Wiernik PH, Testa JR . Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia. Blood 1989; 73: 263–270.

  6. 6

    Dastugue N, Payen C, Lafage-Pochitaloff M, Bernard P, Leroux D, Huguet-Rigal F et al. Prognostic significance of karyotype in de novo adult acute myeloid leukemia. Leukemia 1995; 9: 1491–1498.

  7. 7

    Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi R et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 1998; 58: 4173–4179.

  8. 8

    Hurwitz CA, Raimondi SC, Head D, Krance R, Mirro Jr J, Kalwinsky DK et al. Distinctive immunophenotypic features of t(8;21)(q22;q22) acute myeloblastic leukemia in children. Blood 1992; 80: 3182–3188.

  9. 9

    Kita K, Nakase K, Miwa H, Masuya M, Nishii K, Morita N et al. Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with the stem cell antigen CD34. Blood 1992; 80: 470–477.

  10. 10

    Kita K, Shirakawa S, Kamada N . Cellular characteristics of acute myeloblastic leukemia associated with t(8;21)(q22;q22). The Japanese Cooperative Group of Leukemia/Lymphoma. Leukemia Lymphoma 1994; 13: 2229–2234.

  11. 11

    Nishii K, Kita K, Nadim M, Miwa H, Ohoish K, Yamaguchi M et al. Expression of interleukin-5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype. Br J Haematol 1995; 91: 169–172.

  12. 12

    Andrieu V, Radford-Weiss I, Troussard X, Chane C, Valensi F, Guesnu M et al. Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics, morphology and immunophenotype. Br J Haemotol 1996; 92: 855–865.

  13. 13

    Shikami M, Miwa H, Nishii K, Takahashi T, Sekine T, Mahmud N et al. Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality. Leukemia 1999; 13: 358–368.

  14. 14

    Raspadori D, Damiani D, Lenoci M, Rondelli D, Testoni N, Nardi G et al. CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis. Leukemia 2001; 15: 1161–1164.

  15. 15

    Lorsbach RB, McNall R, Mathew S . Marked bone marrow basophilia in a child with acute myeloid leukemia with a cryptic t(8;21)(q22;q22) chromosomal translocation. Leukemia 2001; 15: 1799–1801.

  16. 16

    Groupe Francais de Cytogenetique Hematogique. Acute myelogenous leukemia with an 8;21 translocation. A report on 148 cases from the Groupe Francais de Cytogenetique Hematologique. Cancer Genet Cytogenet 1990; 44: 169–179.

  17. 17

    Ohno R, Kobayashi T, Tanimoto M, Hiraoka A, Imai K, Asou N et al. Randomized study of indualized induction therapy with or without vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 study of the Japan Adult Leukemia Study Group. Cancer 1993; 71: 3888–3895.

  18. 18

    Kobayashi T, Miyawaki S, Tanimoto M, Kuriyama K, Mueakami H, Yashida M et al. Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. J Clin Oncol 1996; 14: 204–213.

  19. 19

    Miyawaki S, Tanimoto M, Kobayashi T, Minami S, Tamura J, Omoto E et al. No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Int J Hematol 1999; 70: 97–104.

  20. 20

    Kageyama S . Toxicity and safety of JALSG-AML95 study for newly diagnosed adult acute myelogeneous leukemia. LALSG 10-year Anniversary International Symposium, 1997, pp 30–31.

  21. 21

    Sakamaki H, Miyawaki S, Hatake K, Takahashi M, Minami S, Kobayashi T et al. JALSG AML-97 protocol. LALSG 10-year Anniversary International Symposium, 1997, pp 32–34.

  22. 22

    Suzuki A, Kimura Y, Ohyashiki K, Kitano K, Kageyama S, Kasai M et al. Trisomy 10 in acute myeloid leukemia. Three additional cases from the database of the Japan Adult Leukemia Study Group (JALSG) AML-92 and AML-95. Cancer Genet Cytogenet 2000; 15: 141–143.

  23. 23

    Nishii K, Katayama N, Miwa H, Shikami H, Masuya M, Shiku H et al. Survival of human leukaemic B-cell precursors is supported by stromal cells and cytokines: association with the expression of bcl-2 protein. Br J Haematol 1999; 105: 701–710.

  24. 24

    Nishii K, Usui E, Sakakura M, Miyata E, Ride SA, Ford AM et al. Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-expressing leukemia. Cancer Genet Cytogenet 2001; 126: 8–12.

  25. 25

    Nishii K, Katayama N, Miwa H, Shikami M, Usui E, Masuya M et al. Non-DNA-binding Ikaros isoforms gene expressed in adult B-precursor acute lymphoblastic leukemia. Leukemia 2002; 16: 1285–1292.

  26. 26

    Wattjes MP, Krauter J, Nagel S, Heidenreich O, Ganser A, Heil G . Comparison of nested competitive RT-PCR and real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21) positive acute myelogous leukemia. Leukemia 2000; 14: 329–335.

  27. 27

    Nucifora G, Dickstein JI, Torbenson V, Roulston D, Rowley JD, Vardiman JW . Correlation between cell morphology and expression of the AML1/ETO chimeric transcript in patients with acute myeloid leukemia without the t(8;21). Leukemia 1994; 8: 1533–1538.

  28. 28

    Ferrara F, Del Vecchio L . Acute myeloid leukemia with t(8;21)/AML1/ETO: a distinct biological and clinical entity. Haematologica 2002; 87: 306–319.

  29. 29

    Ema H, Kitano K, Suda T, Sato Y, Muroi K, Ohta M et al. In vitro differentiation of leukemic cells to eosinophils in the presence of interleukin-5 in two cases of acute myeloid leukemia with the translocation (8;21)(q22;q22). Blood 1990; 75: 350–356.

  30. 30

    Tatsumi E, Yoneda N, Kawano S, Yamaguchi N, Yabe H, Nagai K et al. Expression of CD7 antigen precludes t(8;21)(q22;q22) chromosome aberration in acute myeloblastic leukemia. Blood 1992; 79: 3092–3093.

  31. 31

    Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y et al. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J 1993; 12: 2715–2721.

  32. 32

    Shimada H, Ichikawa H, Ohki M . Potential involvement of the AML1-MTG8 fusion protein in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia revealed by microarray analysis. Leukemia 2002; 16: 874–885.

  33. 33

    Kawano S, Miyanishi S, Shimizu K, Tanaka K, Okumura A, Ohki M et al. Genetic analysis of 8;21 chromosomal translocation without AML1 gene involvement in MDS-AML. Br J Haematol 1997; 99: 632–640.

  34. 34

    Asou H, Tashiro S, Hamamoto K, Otsuji A, Kita K, Kamada N . Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 translocation. Blood 1991; 77: 2031–2036.

  35. 35

    Mecucci C, Van Orshoven A, Tricot G, Michaux JL, Delannoy A, Van den Berghe H . Trisomy 4 identifies a subset of acute nonlymphocytic leukemias. Blood 1986; 67: 1328–1332.

  36. 36

    Weber E, Nowoty H, Haas OA, Kasparu H, Grois N, Lutz D . Trisomy 4: a specific karyotype anomaly in primary and secondary acute myeloid leukemia. Leukemia 1990; 4: 219–221.

  37. 37

    Wong KF, So CC . Acute myeloid leukemia with concominant trisomies 4 and 10: a distinctive form of myeloid leukemia? Cancer Genet Cytogenet 2001; 127: 74–76.

  38. 38

    Keung Y, Kaplan B, Douer D . Biphenotypic M0 acute myeloid leukemia with trisomy-4. Leukemia Lymphoma 1994; 14: 181–184.

  39. 39

    Baer MR, Stewart CC, Lawrence D, Arthur DC, Byrd JC, Davey FR et al. Expression of the neural cell adhesion molecule CD56 is associated with short remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22). Blood 1997; 90: 1643–1648.

  40. 40

    Sandberg AA, Van den Berghe H, Hecht F . Trisomy 4 in hematologic disorders. Cancer Genet Cytogenet 1987; 26: 175.

  41. 41

    Bonomi R, Le Coniat M, Berger R . Is trisomy 4 a secondary chromosomal abnormality in acute myeloblastic leukemia? Cancer Genet Cytogenet 1995; 79: 186–187.

  42. 42

    Yamamoto K, Nagata K, Kida A, Hamaguchi H, Inagaki K . Karyotypic conversion from trisomy 4 to trisomy 14 during the evolution of therapy-related myelodysplastic syndrome to acute myeloblastic leukemia. Cancer Genet Cytogenet 2002; 132: 83–84.

Download references


Thanks are due to Drs SI Kageyama, M Masuya, K Ohishi, M Yamaguchi, H Mitani, H Araki, M Sakakura, Y Sugimoto (Second Department of Internal Medicine, Mie University School of Medicine, Mie, Japan); K Kawakami, Y Watanabe (Suzuka Gentral Hospital, Mie, Japan); K Oka (Suzuka Kaisei Hospital, Mie, Japan); T. Sekine (Matsusaka Genaral Hospital, Mie, Japan); K Tsuji, S Tamaki (Yamada Red Cross Hospital, Mie, Japan); T Tsukada, H Kihira (Takeuchi Hospital, Mie, Japan); K, Ikeda (Ise Citizen Hospital, Mie, Japan); M Shikami (The Second Department of Internal Medicine, Aich University School of Medicine, Aich, Japan); I Furuta, M Itou (Shinguu Citizen Hospital); M Nomura (Third Department of Internal Medicine, Kyoto Prefectural University of Medicine); and H Tsutani (First Department of Internal Medicine, Fukui Medical University, Fukui, Japan).

This work was supported by research grants from the Ministry of Education, Culture, Sports, Science, and Technology and from the Ministry of Health, Labour, and Welfare, Tokyo, Japan.

Author information

Correspondence to K Nishii.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nishii, K., Usui, E., Katayama, N. et al. Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML. Leukemia 17, 731–737 (2003).

Download citation


  • t(8;21)
  • trisomy 4
  • CD56
  • CD18
  • additional karyotypic aberration

Further reading