Multilineage involvement in the 5q- syndrome: a fluorescent in situ hybridization study on bone marrow smears

A pluripotent progenitor cell was demonstrated to be involved in myelodysplastic syndromes (MDS) with normal karyotype or with numerical chromosome aberrations, but the pattern of lineage involvement by the 5q31 deletion in the 5q- syndrome is unknown. We performed this study in order to define the distribution pattern of the 5q- anomaly better in the non-lymphoid cell compartment

Bone marrow (BM) smears from 8 patients with the 5q- syndrome were studied by a modification of the fluorescent in situ hybridization (FISH) technique that allowed direct visualization of cell morphology. A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used simultaneously in dual-color experiments with a chromosome-5-centromeric probe (Vysis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional internal controls a chromosome-7-centromeric probe and a 7q31 probe were used. To establish the sensitivity limit of this approach 5 normal BM smears were studied. All 8 patients had the 5q- chromosome as the sole anomaly in 45% to 75% of the interphase cells.

For each patient 20-40 erythroblasts were analyzed: they were mostly proerythroblasts and basophilic erythroblasts. In all patients a clone carrying the 5q31 deletion was detected (35-50% of the cells, median 45%). Between 20-50 granulocyte precursors were scored; the 5q31 deletion was found in 40%-50% (median 45%) in all cases. The proportion of neutrophils carrying the 5q deletion was consistently lower than the corresponding value in promyelocytes (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in all patients, the overall incidence of 5q31 deletion was 52-68%. Equal proportions of large multilobular megakaryocytes and hypolobular megakaryocytes characteristic of the 5q- syndrome were scored: the latter cells showed the 5q31 deletion more frequently than the former cells (93.6% vs 19.3% of the cells). In 66% to 100% of the cases (median 83%) a few cells with uncondensed nuclear chromatin pattern, and two or three prominent nucleoli with cytoplasmatic hypogranulation were seen in each sample carrying the 5q31 deletion.

We arrived at the following conclusions: i) the transformation in the 5q- syndrome involves an early progenitor cell retaining the ability to proceed along multiple differentiation pathways; ii) there is a preferential distribution of the 5q31 deletion within immature cells and morphologically abnormal megakaryocytes.