Acute Myeloid Leukemia with Translocations Involving 4q12/PDGFRA: Frequent Involvement of ETV6
Rashmi Kanagal-Shamanna, C Cameron Yin, Ramya Muddasani, Rajyalakshmi Luthra, Jorge Cortes, Zhuang Zuo, Su S Chen, Daniela Hoehn, Lynne V Abruzzo, Roberto N Miranda, L Jeffrey Medeiros, Gary Lu. UT MD Anderson Cancer Center, Houston
Background: The most common abnormality involving chromosome 4q12 in leukemia is the FIP1L1-PDGFRA fusion gene that results from a cryptic deletion. Most of these neoplasms are classified in the 2008 World Health Organization as myeloid and lymphoid neoplasms with eosinophilia and PDGFRA rearrangement. Here we describe cases of acute myeloid leukemia (AML) with isolated chromosomal translocations involving 4q12/PDGFRA rearrangement.
Design: We searched the files for all cases of AML associated with 4q12 translocations identified by conventional cytogenetics. Using fluorescence in situ hybridization (FISH), we confirmed the presence of PDGFRA rearrangement in all cases and attempted to characterize the partner gene. Histologic and immunohistochemical studies were reviewed and correlated with clinical data and outcome collected from medical records.
Results: The study group included 9 cases of AML with translocations involving PDGFRA. There were 6 men and 3 women with a median age of 55 years (range, 17-76). The median blast count at presentation was 42% (range, 20-94%). Anemia was seen in all patients (median, 10 mg/dL; range, 9-12), leukopenia in 6/9 patients (median, 3.0 K/uL; range, 1-33) and thrombocytopenia in 8/9 patients (median, 36 K/uL, range, 14-227). Peripheral blood and bone marrow eosinophilia was observed in 2/11 patients. Trilineage dysplasia was seen in 2/7 cases, one of which had a history of myelodysplastic syndrome. The remaining 2 cases had too few cells to assess for dysplasia. Conventional cytogenetics showed t(4;12)(p12;p13) in 7 cases, t(4;17)(q12;q25) in 1 case, and t(3;4)(p25;q12) in 1 case. FISH proved PDGFRA and ETV6 rearrangement in all 7 cases with t(4;12). 4q12 rearrangement occurred at time of initial presentation in 3 patients, at the time of transformation from MDS to AML in 2 patients and at relapse in 4 patients. Molecular genetic analysis revealed FLT3 mutation in 1/6 patients assessed, and no evidence of RAS (n=5), NPM1 (n=2) and KIT (n=2) mutations. Seven patients died and 2 patients were alive with a median survival of 8.7 months (range, 2.2–36).
Conclusions: AML with chromosome 4q12 translocations are rare, and most frequently partner the PDGFRA locus with ETV6. Unlike FIP1L1-PDGFRA cases, eosinophilia does not appear o be a prominent feature in this subgroup. Chromosome 4q12/PDGFRA rearrangement can occur at initial diagnosis or at relapse. The role of tyrosine kinase inhibitors in this subgroup of patients remains to be assessed.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 214, Tuesday Morning