Abstract
The t(9;22)(q34;q11), generating the Philadelphia chromosome (Ph), is found in more than 90% of patients with chronic myeloid leukemia (CML) and in 15–30% of adults with acute lymphoblastic leukemia (ALL). Different groups have recently described the presence of large genomic deletions adjacent to the translocation breakpoint on the derivative chromosome 9 in 9–16% of CML patients. In the present paper, we report a FISH study of 45 Ph+ adult ALL patients with the aim of investigating the presence of deletions on derivative chromosome 9. In four (9%) of 45 cases, all showing an M-bcr, we detected deletions on der(9). The frequency of deletions we observed is similar to that reported in CML patients. The association of an M-bcr breakpoint and deletions appears significant (P=0.03). Some authors have suggested a very low incidence of der(9) deletions in ALL. This discrepancy can be explained by taking into account the low percentage of M-bcr ALL patients in the latter study (18%) compared to the present one (44%).
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References
Rowley JD . A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giesma staining. Nature 1973; 243: 290–293.
Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV . Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 1991; 5:196–199.
Shtivelman E, Lifshitz B, Gale RP, Canaani E . Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985; 315: 550–554.
Yokohama A, Karasawa M, Okamoto K, Sakai H, Naruse T . ALL and CML-type BCR/ABL mRNA transcripts in chronic myelogenous leukemia and related disorders. Leuk Res 1999; 23: 477–481.
Saglio G, Pane F, Martinelli G, Guerrasio A . BCR/ABL rearrangement and leukemia phenotype. Leukemia 1999; 13 (Suppl 1): S96.
Deininger MWN, Goldman JM, Melo JV . The molecular biology of chronic myeloid leukemia. Blood 2000; 96: 3343 3356.
Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000; 95: 738–743.
Kolomietz E, Al-Maghrabi J, Brennan S, Karaskova J, Minkin S, Lipton J et al. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Blood 2001; 97: 3581–3588.
Huntly BJ, Reid AG, Bench AJ, Campbell LJ, Telford N, Shepherd P et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood 2001; 98: 1732–1738.
Storlazzi CT, Specchia G, Anelli L, Albano F, Pastore D, Zagaria A et al. Breakpoint characterization of der(9) deletions in CML patients. Genes, Chromosomes Cancer 2002; 35: 271–276.
Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D et al. Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype–phenotype correlations. Hum Mol Genet 1999; 8: 2359–2368.
Haase D, Binder C, Bunger J, Fonatsch C, Streubel B, Schnittger S et al. Increased risk for therapy-associated hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1. Leuk Res 2002; 26: 249–254.
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B . A model for p53-induced apoptosis. Nature 1997; 389: 300–305.
Reid AG, Huntly BJ, Hennig E, Niederwieser D, Campbell LJ, Bown N et al. Deletions of the derivative chromosome 9 do not account for the poor prognosis associated with Philadelphia-positive acute lymphoblastic leukemia. Blood 2002; 99: 2274–2275.
Cook WD, McCaw BJ . Accomodating haploinsufficient tumor suppressor genes in Knudson's model. Oncogene 2000; 19: 3434–3438.
Gleißner B, Gökbuget N, Bartram CR, Janssen B, Rieder H, Janssen JWG et al. Leading prognostic relevance of the BCR–ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002; 99: 1536–1543.
Acknowledgements
The financial support of Associazione Italiana per Ricerca contro il Cancro (AIRC), CEGBA, MIUR (Ministero Istruzione Università e Ricerca), CNR (Centro Nazionale della Ricerca), and FIRB-MIUR (Fondo Investimento Ricerca Biologica) is gratefully acknowledged.
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Specchia, G., Albano, F., Anelli, L. et al. Deletions on der(9) chromosome in adult Ph-positive acute lymphoblastic leukemia occur with a frequency similar to that observed in chronic myeloid leukemia. Leukemia 17, 528–531 (2003). https://doi.org/10.1038/sj.leu.2402829
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DOI: https://doi.org/10.1038/sj.leu.2402829