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Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and risk for evolving to acute leukemia. Some molecular abnormalities related to acute myeloid leukemia (AML) transformation have been reported, such as FLT3 (FMS-like tyrosine kinase 3) mutations. FLT3, a member of the class 3 receptor tyrosine kinase family, mediates stem cell proliferation and differentiation, and its mutations, internal tandem duplication (ITD) and Asp835, have been reported in rare MDS patients. We studied FLT3 ITD, prospectively, in 50 MDS patients at diagnosis, at 6 and 12 months follow-up, and at any other time-point if AML transformation was detected. FLT3 ITD was not observed at diagnosis, but during follow-up the mutation was present in 2 of 50 patients (4%). Of these, one case exhibited FLT3 ITD at the end of the 6 months of follow-up in approximately 8% of bone marrow cells; this case evolved into AML at 8 months, at which time FLT3 ITD was present in approximately 85% of bone marrow cells. The other case exhibited FLT3 ITD in 68% of bone marrow cells at 7 months, precisely at the time of AML transformation. Although rare in MDS, FLT3 ITD is associated with a high probability of evolution to AML.

Poor outcomes of some chronic myeloid leukemia ((CML) patients have been associated with submicroscopic der(9q) deletions, particularly the 5′ ABL region. Deletion profiles of 120 BCR/ABL+ CML patients were studied using the dual-fusion fluorescence in situ hybridization probe. Poor prognosis was associated with 5′ ABL deletion but not with 3′ BCR deletion. Overall survival (OS) and chronic phase duration (CPD) were significantly shorter for 5′ ABL deletion than for those without deletions (OS time: 27 vs. 61 months, P = 0.02; CPD: 17 vs. 56 months, P = 0.02). In addition, when isolated 5′ ABL deletion patients were compared to those without it, a greater impact on prognosis was detected (OS time: 18 vs. 59 months, P = 0.0008; CPD: 7 vs. 54 months, P = 0.0003). Isolated 5′ ABL deletion seems to have a greater impact on survival than does concomitant 5′ ABL and 3′ BCR deletion, although the difference was not statistically significant in this aspect (OS time: 18 vs. 28 months, P = 0.08).

Universidade Federal de Sao Paulo, Disciplina Hematol & Hemoterapia, Escola Paulista Med, EPM, BR-04023900 Sao Paulo, Brazil