CLONAL EVOLUTIONS DURING LONG-TERM CULTURES OF BONE-MARROW FROM DENOVO ACUTE MYELOID-LEUKEMIA WITH TRILINEAGE MYELODYSPLASIA AND WITH MYELODYSPLASTIC REMISSION MARROW

We previously established a long-term bone marrow culture (LTBMC) syst em in which novel abnormal karyotypes could emerge in vitro prior to t he appearance of the same karyotypes in vivo in patients with myelodys plastic syndrome (MDS). We extended our study to examine whether acute myeloid leukaemia (AML) transformed from MDS (MDS/AML) and de novo AM L with trilineage myelodysplasia (AML/TMDS) show clonal evolution in L TBMC similar to that of typical AML or MDS. We also analysed the cytog enetic changes in cultures with bone marrows from AML with myelodyspla stic remission marrow (AML/MRM) as well as chronic myeloid leukaemia ( CML) to compare them with typical AML with respect to the liability of clonal evolution. Among the 34 AML cases, abnormal karyotypes were ne wly detected in four of seven MDS/AML, three of six AML/TMDS and three of three AML/MRM. Novel abnormal karyotypes were also observed in nin e out of 13 CML cases after culture. In contrast, no other abnormal ka ryotypes were found after culture in 18 typical AML without myelodyspl asia. These findings suggest that AML/TMDS and AML/MRM are different f rom typical AML and are similar to MDS/AML and CML in view of their po tential for disease progression from latent multiple clones. Typical A ML may develop from a single abnormal clone without any subclones.