Delineation by molecular cytogenetics of 5q deletion breakpoints in myelodyplastic syndromes and acute myeloid leukemia

Deletions of 5q in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are of different extents and the majority map to sub-bands 5q13.3 and 5q33.1. To further pinpoint these deletions, we have performed a detailed interphase fluorescence in situ hybridization (I-FISH) analysis with precisely mapped BAC probes. Eleven MDS and two AML patients with a sole cytogenetically visible del(5q) were studied. The proximal deletion endpoints were localized between 75 and 86 megabases (Mb) (5q13, five times), 86 and 96 Mb (5q14∼q15, four times), and at various sites in the other four. The distal breakpoints mapped between 153 and 155 Mb (5q33.2, five times), 156 and 158 Mb (5q33.3, three times), 158 and 164 Mb (5q34, two times), and 164 and 181 Mb (telomere) in three. The largest deletion was approximately 70 Mb and the smallest was 43 Mb. These studies show that cytogenetically similar appearing deletions in 5q are highly variable in molecular terms. We also found that in MDS cases with a blast count between 0 and 13%, cells with a del(5q) were present in 24–90% of interphase (nondividing) cells and in 30–100% of metaphase (dividing) cells. In the two AML patients with a blast count of 30 and 80%, del(5q) was found in 35 and 95% interphase cells and 95 and 100% of metaphase cells, respectively. This demonstrates that a low blast count can be associated with a high proportion of 5q− cells in the bone marrow.