Minimally differentiated acute myeloid leukemia (AML-M0) with lymphoid presentation at relapse: a case report

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Recently, Iwata et al 1 reported a case of T-ALL misdiagnosed as AML-M0, thus pointing out the limitations of the diagnostic criteria for this immature leukemia. The FAB cooperative group defined guidelines in 1991: AML-M0 diagnosis require negative myeloperoxidase (MPO) and Sudan Black B (SBB) staining, positive myeloid markers (usually CD13 and 33, but also CD14, CD15, CD11b) and negative T and B associated markers.2 Since then, many authors shaped these guidelines into a new definition, in which some lymphoid antigens were not considered as exclusion criteria anymore, albeit negativity for cytoplasmic CD3 (cCD3), cCD22 and CD79a remains compulsary to avoid misdiagnosis with biphenotypic acute leukemia. This immunological classification of AML-M0 was supported by the proposition of the EGIL.3

Nevertheless, AML-M0 is heterogenous with respect to immunophenotyping and cytogenetics and we are still lacking a specific marker to single out this sybtype as an entity distinct from the other immature leukemias.

A 19-year-old man was referred to our institution in July 1999 for fever and asthenia. The white blood cell count was reduced to 1.5 × 106/l without abnormal cells, and anemia was also noticed. Bone marrow aspiration revealed infiltration with 80% blast cells, without myelodysplastic features in the remaining cell population. Less than 3% of these blasts were MPO+, none was butyrate esterases +, upon staining. Flow cytometric analysis was performed on total bone marrow using a CD45 monoclonal antibody. The blast cells were positive for CD15, CD65, CD4, CD11b, CD11c, CD16, cMPO, CD36, GlycoA, CD133, CD61, CD71, but negative for CD34, CD13, CD33, CD2, CD3, CD7, CD5, CD8, CD10, CD19, CD20, cCD22, CD79a, cCD3, TdT, CD41, CD56, CD117 (see Table 1). The karyotype of the leukemic cells revealed: 46 XY, der (10), der(11) t(11;19)(p11;?), der(19)t(11;19), der(?)t(?;19). Hybridization of a MLL probe showed no chromosomal alteration involving 11q23. The patient was diagnosed with AML-M0 based on FAB criteria, and received standard induction therapy. Complete cytologic and karyotypic response was achieved after the first course of chemotherapy, and double autologous BMT was proposed as a consolidation therapy in the absence of an HLA-matched donor. Treatment was completed in January 2000.

Table 1 Immunophenotyping of blast cells at diagnosis and at the time of relapse

In November 2000, thrombocytopenia necessitated that a new bone marrow aspiration and trephine biopsy be performed, which confirmed the relapse of the acute leukemia with 80% of infiltrating blastic cells, but with lymphoblastic cytologic and cytochemistry features (MPO negative): cytometric analysis revealed positivity for lymphoid markers (see Table 1), arguing for the diagnosis of B-III acute lymphoid leukemia (ALL) according to the EGIL classification.3 There was only one blastic population in the blast gate, as already noticed at the time of diagnosis of AML 1 year before. It is of note that the karyotype of the blasts exhibited the same t(11;19) as at the time of the onset of the disease, thus proving that the B-ALL emerged from the same leukemic clone that previously developed into AML. The patient subsequently received induction therapy for ALL, and once again complete response was achieved, with disparition of karyotypic abnormalities. He is now receiving consolidation therapy for ALL.

Initial diagnosis of AML-M0 may first of all be a matter of controversy, as the phenotypic profile was not that of an immature proliferation. Some authors are cautious with the interpretation of MPO in the absence of CD13 and 33 positivity, arguing that with flow cytometric analysis, methodological bias in the immunostaining procedure may confer false MPO positivity to genuine ALL blasts. However, in our case, none of the usual surface of intracytoplasmic lymphoid marker was found, and CD15, CD65 and CD133 confirmed the myeloid lineage of the cells. Moreover, negative and positive controls with our anti-MPO antibody proved reliable with efficient and accurate results.

Venditti et al 4 reported up to 16% AML-M0 negative for CD13 and CD33, CD15 being the only surface myeloid-associated antigen in one case. In the same study, the authors also show that CD13 and CD33 negative blasts are only seen in AML-M0. Some blasts were CD4 and CD11c positive, suggesting that some AML-M0 may in fact be immature AML-M5, but these antigens are expressed at a weaker level in M0 cases, as in our patient. A misprogramming of the differentiation pathway (lineage infidelity) of a multipotent stem cell could argue for CD4 positivity in AML-M0. However, the stem cell pattern associating TdT and CD34 positivity, 5q and 7q deletions and complex karyotype defined by Venditti et al 4 in the majority of AML-M0 cases, was not seen in our patient. This suggests that the first clonal disease may arise as part of an immature monocytic proliferation, or that blasts showed minimal phenotypic deviation. The latter assumption is likely to be conforted by the lymphoid (and not monocytic) presentation at relapse, whereas GlycoA, CD36 and CD61 positivity, which is only sporadically reported in case series of AML-M0 in the literature, was presumably linked to platelet and red cells debris adherence to blasts (as histogram analysis showed only weak expression of these antigens), by means of CD15 expression by blasts.5

According to Kotylo et al,6 one could also consider that the blasts of our patient at diagnosis displayed a pediatric-like M0 phenotypic profile (TdT, CD34, CD7, CD13, CD15+, CD11b+ and 11c+), except the absence of a bright expression of CD33. However, neither AML-M0 relapsing as B-ALL, nor the presence of a balanced translocation t(11;19) which appears to be the clonal marker of the immature leukemic proliferation in our case have been reported in children or adults before. To our knowledge, this is the first reported case of AML-M0 with such atypical cytogenetics and immunophenotyping presentation.

Thus, elucidating the mechanisms of leukemogenesis in multipotent precursors is of particular importance to provide new tools to diagnose AML-M0 as a distinct entity among acute undifferentiated leukemias. In our case, the bilineage differentiation ability of the blasts contrasted with their unusual phenotypic profile, and this new t(11;19)(p11;?) could stand for a marker of immaturity, like 11q23 rearrangements and t(9;22), contrasting with a quite good response to chemotherapy at least during induction therapy.


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Correspondence to M Maynadié.

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Ysebaert, L., Carli, P., Casasnovas, R. et al. Minimally differentiated acute myeloid leukemia (AML-M0) with lymphoid presentation at relapse: a case report. Leukemia 15, 1673–1674 (2001) doi:10.1038/sj.leu.2402240

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