Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia

Several studies have demonstrated the prognostic value of cytogenetic analy sis in MDS both for survival and progression to AML. However it is unknown which are the numerical or structural abnormalities required for leukemic t ransformation. In this report we studied clinically and cytogenetically 127 patients: 125 with primary MDS and two with AML with a previous history of MDS. Thirty-one patients (24%) showed evolution of the disease during the follow-up study. Chromosomal abnormalities found at diagnosis in patients t hat progressed toward AML included: del(5)(q15), +6, del(6)(q21), t(5;8)(q3 2;q22),-7, del(7)(q22), der(7)t(1;7)(q10;p10), t(7;11)(p15;p15), + 8, del(1 1)(q23), del(12p), del(3)(q21), del(20)(q12) and complex karyotypes. Eight of these patients were studied cytogenetically during transformation and sh owed acquisition of chromosomal alterations involving dup(1q), + 8, del(11) (q23), and translocations between chromosomes 1 and 8 or 7 and 17. In addit ion we also observed gain of ploidy and monosomy 21. These results suggest that chromosomal alterations during evolution of the disease include specia l chromosome gains or abnormalities of chromosomes 1, 7, 8, 11 and 17 with involvement of ETV-1, Hox-A9, Pax 4, MLL genes besides a putative gene mapp ed at 17q25. We also applied the International Prognostic Scoring System (I PSS) to 114 patients, excluding those submitted to allogeneic bone marrow t ransplant. Our patients were classified into four distinct risk groups. The analysis of risk groups presented by 27 patients who showed evolution of t he disease revealed 18 at the high risk group and four at the intermediate- 2 group. From the intermediate-1 risk group only five patients showed evolu tion of the disease. Three of these patients evolved from RA to RAEB with g ain of a del(11)(q23) or an expansion of a del(12)(p12) clone. Our results suggest that some chromosomal alterations are responsible for each step in the evolution of the disease. As the pathway of evolution is not unique it has been very difficult to define what genetic alteration comes first. Howe ver from several results in the literature and our own, it seems that some chromosomal alterations may predict the evolution of the disease and are co rrelated with short survival, as for example the trisomy of chromosome 8, a nd might be incorporated in the high risk group in the IPSS. This score sys tem has been proved to be useful for predicting survival and evolution from MDS to AML. (C) 2000 Elsevier Science Ltd. All rights reserved.