Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations

• Published in: Blood Vol. 124; no. 24; pp. 3577 - 3582
• Main Authors: La Starza, Roberta, Borga, Chiara, Barba, Gianluca, Pierini, Valentina, Schwab, Claire, Matteucci, Caterina, Lema Fernandez, Anair G., Leszl, Anna, Cazzaniga, Gianni, Chiaretti, Sabina, Basso, Giuseppe, Harrison, Christine J., te Kronnie, Geertruy, Mecucci, Cristina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.12.2014
• Subjects: Adolescent; Adult; Child; Child, Preschool; Chromosomes, Human, Pair 6 - genetics; Chromosomes, Human, Pair 6 - metabolism; Chromosomes, Human, Pair 7 - genetics; Chromosomes, Human, Pair 7 - metabolism; Disease-Free Survival; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Humans; Hyaluronan Receptors - biosynthesis; Hyaluronan Receptors - genetics; Male; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Survival Rate; Translocation, Genetic; Trisomy - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-06-578856

MYC translocations represent a genetic subtype of T-lineage acute lymphoblastic leukemia (T-ALL), which occurs at an incidence of ∼6%, assessed within a cohort of 196 T-ALL patients (64 adults and 132 children). The translocations were of 2 types; those rearranged with the T-cell receptor loci and those with other partners. MYC translocations were significantly associated with the TAL/LMO subtype of T-ALL (P = .018) and trisomies 6 (P < .001) and 7 (P < .001). Within the TAL/LMO subtype, gene expression profiling identified 148 differentially expressed genes between patients with and without MYC translocations; specifically, 77 were upregulated and 71 downregulated in those with MYC translocations. The poor prognostic marker, CD44, was among the upregulated genes. MYC translocations occurred as secondary abnormalities, present in subclones in one-half of the cases. Longitudinal studies indicated an association with induction failure and relapse. •MYC translocations represent a genetic subgroup of NOTCH1-independent T-ALL clustered within the TAL/LMO category.•MYC translocations are secondary abnormalities, which appear to be associated with induction failure and relapse.