ABL oncogene amplification with p16(INK4a) gene deletion in precursor T-cell acute lymphoblastic leukemia/lymphoma: report of the first case.
Gene amplification is a relatively rare event in hematologic malignancies. The ABL gene on chromosome band 9q34 is a proto-oncogene and is the well-known translocation partner of the BCR gene on 22q11 giving rise to t(9;22)(q34;q11), which is the hallmark of chronic myeloid leukemia and is the most common chromosomal abnormality in adult acute lymphoblastic leukemia (ALL). Amplification of ABL is an exceedingly rare event, with only less than 5 cases reported in the literature. The p16(INK4a) (or CDKN2A) gene on 9p21 is a tumor suppressor gene, and deletion thereof is recently recognized as one of the most common genetic abnormalities in ALL. The authors herein describe an 8-year-old male patient with precursor T-cell ALL harboring both ABL gene amplification and p16(INK4a) gene deletion. Fluorescence in situ hybridization (FISH) analysis using BCR/ABL probes revealed five or more ABL signals, indicating amplification in 51.5% of interphase nuclei. FISH using p16(INK4a) gene probes showed heterozygous p16(INK4a) deletion in 71.0%. On conventional cytogenetic analysis, however, only 10 metaphases were available, which showed the normal karyotype, 46,XY[10], serving no evidence for the findings on FISH. This is the first report of an ALL case with ABL amplification, and the authors speculate that both ABL proto-oncogene amplification and the p16(INK4a) tumor suppressor gene deletion have been implicated in leukemogenesis in the present case, although whether the ABL amplification truly contributes to the leukemogenesis or merely an epiphenomenon representing underlying genomic instability remains to be determined.
Kim
Hee-Jin
HJ
Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Woo
Hee-Yeon
HY
Koo
Hong-Hoe
HH
Tak
Eun-Young
EY
Kim
Sun-Hee
SH
D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics* / Q000648:ultrastructure; D005784:Gene Amplification; D017353:Gene Deletion; D016313:Genes, abl; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas