Microarray analyses of T-ALL (COG study)

The clinical and cytogenetic features associated with T-cell acute lymphoblastic leukemia (T-ALL) are not predictive of early treatment failure or relapse. We used the Affymetrix U133 Plus 2.0 chip to profile 100 newly diagnosed patients who were treated in the Children's Oncology Group (COG) T-ALL AALL0434. We performed unsupervised hierarchical clustering of 25 HOXA probe sets within the cohort of 100 T-ALL cases. We identified a cluster of 20 cases (20%) characterized by increased expression of HOXA3, 5, 7, 9, and 10. In samples with HOXA9/10 deregulation, the presence of specific molecular lesions were confirmed through a systematic review of cytogenetic databases, FISH and PCR testing, and by RNA sequence analysis. Because MLL and AF10 genes rearrangements (MLL-R, AF10-R) are hallmarks of HOXA-deregulated leukemias, we sought to identify specific genes that are enriched with these genomic abnormalities.

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Matlawska-Wasowska K, Kang H, Devidas M, Wen J, Harvey RC, Nickl CK, Ness SA, Rusch M, Li Y, Onozawa M, Martinez C, Wood BL, Asselin BL, Chen IM, Roberts KG, Baruchel A, Soulier J, Dombret H, Zhang J, Larson RS, Raetz EA, Carroll WL, Winick NJ, Aplan PD, Loh ML, Mullighan CG, Hunger SP, Heerema NA, Carroll AJ, Dunsmore KP, Winter SS