Frequency, hematopathology, and detection of a new isodicentric variant of deletion 20q.

The ider(20)(p11.21)del(20)(q11q13) anomaly was recognized only recently. Thus, its frequency and clinical significance has not been extensively studied. Due to small size and ambiguous G-band pattern, ider(20q) is usually missed in cytogenetic studies. Furthermore, the commercial FISH probe D20S108 does not distinguish among del(20q), ider(20q), and monosomy 20. Thus, we determined the frequency and hematopathology of patients with ider(20q), and the best cytogenetic methods to detect chromosome 20 anomalies. To do this, we performed FISH on interphase and metaphase cells for 12 patients with -20,+mar and 12 patients with only del(20q) in their karyotype. The marker chromosome in patients with -20,+mar proved to be ider(20q). FISH with D20S108 and 20qter distinguished ider(20q) from del(20q) and monosomy 20. Review of blood and bone marrow slides for nine patients with ider(20q) showed that one had acute myeloid leukemia and eight had myelodysplastic syndromes. Patients with ider(20q) had a more consistent presentation of multilineage dysplasia with additional involvement of the granulocytic series than patients with del(20q). This study shows ider(20q) is common in clinical practice--1/10th the incidence of del(20q)--and is strongly associated with myelodysplasia and acute myeloid leukemia.

Development of five dual-color, double-fusion fluorescence in situ hybridization assays for the detection of common MLL translocation partners.

Chromosomal rearrangements involving the mixed lineage leukemia (MLL) gene at 11q23 are frequent in adult and childhood acute leukemia and have been associated with an unfavorable prognosis. Recent evidence suggests that MLL gene partners may influence prognosis. Five translocations account for approximately 80% of MLL rearrangements: t(4;11)(q21;q23), AFF1/MLL; t(6;11)(q27;q23), MLLT4/MLL; t(9;11)(p22;q23), MLLT3/MLL; t(11;19)(q23;p13.1), MLL/ELL; and t(11;19)(q23;p13.3), MLL/MLLT1. We have designed dual-color, double-fusion fluorescence in situ hybridization (D-FISH) probe sets to identify these translocations. A blinded study was performed for each probe set using 25 normal bone marrow samples, 25 t(4;11), 20 t(6;11), 20 t(9;11), 18 t(11;19p13.1), and 20 t(11;19p13.3) leukemia specimens as defined by chromosome analysis. The findings demonstrated abnormal D-FISH results for 24 of 25 AFF1/MLL, 19 of 20 MLLT4/MLL, all 20 MLLT3/MLL, all 18 MLL/ELL, and all 20 MLL/MLLT1 samples, confirming the efficacy of these D-FISH assays in detecting these common MLL/partner translocations. Our D-FISH assays were more accurate than chromosome analysis at distinguishing disruption of 19p13.1/ELL from that of 19p13.3/MLLT1. We also demonstrated a statistically significant increase in complex/unbalanced MLL/partner translocations occurring in pediatric patients versus adult patients (P = 0.02). A normal cutoff of 0.6% was established, suggesting an application for these assays in minimal residual disease detection and disease monitoring.