FISH Is Necessary To Distinguish MLLT10/MLL Fusion from MLLT10/CALM Fusion in Acute Leukemia with Chromosome 10p and 11q Rearrangements.
William R Sukov, Ryan A Knudson, Jeannette G Keefe, Rhett P Ketterling. Mayo Clinic, Rochester, MN
Background: The MLLT10 gene at 10p13 was initially identified as a fusion partner with MLL in the recurrent t(10;11)(p13;q23) in AML and less frequently ALL, and is associated with an unfavorable prognosis. A second 10;11 translocation resulting in fusion of MLLT10 with the CALM gene at 11q21 was subsequently identified in T-cell ALL, and rarely AML, and has a more favorable prognosis. Unfortunately, the close proximity of the MLL and CALM genes on chromosome 11q, and the complexity of structural rearrangements resulting in MLLT10/MLL or MLLT10/CALM fusion, precludes their differentiation by chromosome studies alone.
Design: To specifically identify fusion of MLLT10/MLL versus MLLT10/CALM, we have developed two dual-color, double-fusion FISH (D-FISH) probe sets. Following IRB approval, we identified 40 patients with bone marrow chromosome studies demonstrating concurrent structural abnormalities involving chromosome 10p and chromosome 11q.
Results: Using the MLLT10/MLL probe set, we identified 20 samples with MLLT10/MLL fusion. Of these cases, the chromosome 10 breakpoint was variably described, including 10 cases at 10p13, with the remaining 10 cases described from 10p11.2 to 10p15. The chromosome 11 breakpoint was most frequently described at 11q23 (15 cases), with 4 cases described at 11q13 and 1 cases at 11q21. Of these 20 patients with MLLT10/MLL fusion, 16 patients demonstrated a D-FISH signal pattern suggesting a complex translocation, with only 4 patients demonstrating a signal pattern indicating an apparently balanced 10;11 translocation.
FISH testing of the remaining 20 samples with the MLLT10/CALM probe set identified 8 samples with MLLT10/CALM fusion. Of these 8 specimens, 3 were described as a t(10;11)(p13;q21), 1 as a t(10;11)(p15;q21), 1 as an add(10)(p11.2) and an add(11)(q13), 1 as an add(10)(p11.2) and a del(11)(q23), 1 as an add(10)(p13) with monosomy 11, and 1 as a t(10;11)(p11.2;q13). Of these 8 specimens, 7 demonstrated a D-FISH signal pattern consistent with a balanced 10;11 translocation.
Conclusions: The present findings suggest that bone marrow samples with concurrent 10p and 11q abnormalities should be evaluated to determine the presence of either MLLT10/CALM or MLLT10/MLL fusion. Based on the frequency of atypical D-FISH signal patterns and the various cytogenetic descriptions for these two recurrent 10;11 translocations, we believe FISH testing is warranted to specifically distinguish these prognostic abnormalities in patients with acute leukemia.
Monday, February 28, 2011 1:00 PM
Poster Session II # 183, Monday Afternoon