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

Background and Objectives. A pluripotent progenitor cell was demonstrated t o be involved in myelodysplastic syndromes (MDS) with normal karyotype or w ith numerical chromosome aberrations, but the pattern of lineage involvemen t by the 5q31 deletion in the 5q- syndrome is unknown. We performed this st udy in order to define the :distribution pattern of the 5q- anomaly better in the nonlymphoid cell compartment. Design and Methods. Bone marrow (BM) smears from 8 patients with the 5q- sy ndrome were studied by a modification of the fluorescent in situ hybridizat ion (FISH) technique that allowed direct Visualization of cell morphology, A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used simulta neously in dual-color experiments with a chromosome-5-centromeric probe (Vy sis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional internal controls a chromosomo-7-centromeric probe and a 7q31 probe were us ed. To establish the sensitivity limit of this approach 5 normal : BM smear s were studied. All 8 patients had the 5q- chromosome as the sole anomaly i n 45% to 75% of the interphase cells. Results. For each patient 20-40 erythroblasts were analyzed: they were most ly proerythroblasts and basophilic erythroblasts, In all patients a clone c arrying the 5q31 deletion was detected (35-50% of the cells, median 45%). B etween 20-50 granulocyte precursors were scored; the 5q31 deletion was foun d in 40%-50% (median 45%) in all cases. The proportion of neutrophils carry ing the 5q deletion was consistently lower than the corresponding value in promyelocytes (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in a ll patients, the overall incidence of 5q31 deletion was 52-68%, Equal propo rtions 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 uncondens ed nuclear chromatin pattern, and two or three prominent nucleoli with cyto plasmatic hypogranulation were seen in each sample carrying the 5031 deleti on. Interpretation and Conclusions. We arrived at the following conclusions: i) the transformation in the 5q- syndrome involves an early progenitor cell r etaining the ability to proceed along multiple differentiation pathways; ii ) there is a preferential distribution of the 5031 deletion within immature cells and morphologically abnormal megakaryocytes, (C) 2001, Ferrata Stort i Foundation.