MYELODYSPLASTIC SYNDROME ACUTE MYELOID-LEUKEMIA SUPERVENING PREVIOUSLY UNTREATED CHRONIC B-LYMPHOCYTIC LEUKEMIA - DEMONSTRATION OF THE CONCOMITANT PRESENCE OF 2 DIFFERENT MALIGNANT CLONES BY IMMUNOLOGICAL AND MOLECULAR ANALYSIS

The development of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML) has rarely been observed in patients with chronic B-ly mphocytic leukemia (B-CLL). So far, the discussion concerning the path ogenesis of the simultaneous occurrence of these two malignancies has been speculative, opposing the theory of two separate malignant clones to the theory of a common stem cell malignancy. We describe the case of a 77-year-old woman who developed MDS after a years of an indolent course of B-CLL. The diagnosis of MDS was based on bone marrow (BM) mo rphology, showing the typical picture of a refractory anemia with exce ss of blasts (RAEB). The clinical course of MDS was aggressive, termin ating in AML within only 6 months. Immunophenotyping of BM and periphe ral blood (PB) cells revealed a CD34(+)/CD13(+)/CD33(-)/CD19(-) blast cell population and a CD19(+)/CD5(+) B-cell population with kappa ligh t chain restriction. Molecular analysis of PB and BM demonstrated the presence of an immunoglobulin heavy chain (IgH) gene rearrangement by polymerase chain reaction (PCR) amplification of genomic DNA with thre e different pairs of consensus primers. Cell-sorting experiments showe d that the IgH gene rearrangement. was present only in the CD19(+)/CD3 4(-) B-cell population, but not in the CD34(+)/CD19(-) blast cells. Fu rthermore, X-chromosome inactivation pattern analysis revealed two dif ferently methylated cell populations. These experiments demonstrate th e concomitant existence of two different clones in a patient with CLL- MDS/AML.