कार्सिनोजेनेसिस और उत्परिवर्तन जर्नल

अमूर्त

5q- Syndrome in Transformation to the Philadelphia Chromosome Positive Acute Myeloblastic Leukemia

Ana Vidovic, Gradimir Jankovic, Nada Suvajdžic Vukovic, Ziv Radisavljevic, Jelica Jovanovic, Marija Dencic Fekete, Biljana TodoricŽivanovic, Irena Ðunic, Jelena Bila, Nataša Colovic and Dragica Tomin

Background: A rare 5q- syndrome subtype (OMIM:153550) of the myelodysplastic syndrome (MDS) evolved to the Philadelphia (Ph) chromosome positive acute myeloblastic leukemia (AML) is presented. The MDS is an acquired clonal stem cell disorder frequently associated with a variety of chromosomal abnormalities. The most common karyotype abnormalities in MDS are del(5q), -7 and +8. The t(9;22)(q34;q11) results in the formation of the Ph chromosome and generates an active chimerical BCR-ABL tyrosine kinase most commonly associated with chronic myelogenous leukemia (CML) and adult precursor B-acute lymphoblastic leukemia (B-ALL). The Ph chromosome positive MDS and AML are uncommon with only 1-2% of newly diagnosed cases. Case report: We present a 72-year old woman with MDS. The HG-banding technique applied on unstimulated bone marrow cells showed 46,XX,del(5)(q13q33)[10]/46,XX. Ten months later, the white blood cell (WBC) count increased to 72×109/l, with 60% of myeloblasts in the formula. The bone marrow aspirate was hypercellular with 50% blasts. The cytogenetic study demonstrated the presence of Ph chromosome together with the initial del(5q) in the same cellular clone. Chemotherapy with hydroxyurea and low-dose cytosine arabinoside was followed by an increase in WBC count to 98×109/l. The dosage of cytosine arabinoside was escalated to 100 mg/m2, for 7 days resulting in a drop in the WBC count to 12×109/l. The follow-up bone marrow aspirations showed a further progression of disease with >70% of myeloblasts in the myelogram. The patient lived 10 months after the initial diagnosis of MDS was made and another 4 months after the diagnosis of secondary AML. Conclusion: The karyotype evolution from the solely 5q- to the 5q- and Ph-positive clone in the MDS in transformation to secondary AML (sAML) is a rare event. To our knowledge, this is a second such case reported in the literature. Based on current literature, we discuss possible links between the 5q- syndrome, BCR/ABL-negative chronic myeloproliferative neoplasms and the BCR/ABL-positive leukemias.