Complex cytogenetics in a case of probably work related MDS/AML

In the majority of cases of overt acute myeloid leukemia (AML), there is no knowledge about a preleukemic phase of myelodysplastic syndrome (MDS). A few recent case-control studies suggest an association between MDS and several occupations. We report a unique case of MDS/AML related to the patient’s work condition with numerous cytostatic agents. The karyotype revealed a spectrum of genetic rearrangements identified by conventional cytogenetics, fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY). We suggest that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized previously.     

ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR–ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.