Abstract
The recurring translocation t(10;11)(p13;q14) which is found in acute myeloid leukemia (AML) and in acute lymphoblastic leukemia (ALL) results in the fusion of the putative transcription factor AF10 to CALM encoding a clathrin assembly protein. Previous studies using mainly fluorescence in situ hybridization (FISH) analysis have shown that the CALM/AF10 rearrangement is found in immature acute myeloid leukemia (AML) of subtype M0 and M1 and in T cell ALL. In this study we analyzed the CALM/AF10 and AF10/CALM fusion mRNAs in a series of three patients with AML, one patient with T-ALL and two patients with precusor T lymphoblastic lymphoma. In all six patients the breakpoint in CALM is at the 3′ end of the coding region (nt1926/1927 or nt 2091/2092). Three breakpoints could be identified in AF10 (nt 588/589, nt 882/883 and nt 978/979). These data demonstrate that the CALM/AF10 fusions found in patients differ only slightly with respect to the portion of AF10 present and that there is no obvious difference between the fusions found in AML patients compared to those found in patients with lymphoid malignancies.
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References
Rowley JD . Recurring chromosome abnormalities in leukemia and lymphoma Semin Hematol 1990 27: 122–136
Rabbitts T . Chromosome translocations in human cancer Nature 1994 372: 143–149
Fischkoff SA, Testa JR, Schiffer CA . Acute eosinophilic leukemia with a (10;11) chromosomal translocation Leukemia 1988 2: 394–397
Hematologique GFdC . t(10;11)(p13–14;q14–21): a new recurrent translocation in T-cell acute lymphoblastic leukemias Genes Chromosomes Cancer 1991 3: 411–415
Secco C, Wiernik PH, Bennett JM, Paietta E . Acute leukemia with t(10;11)(p11–p15;q13–q23) Cancer Genet Cytogenet 1996 86: 31–34
Dreyling MH, Martinez-Climent JA, Zheng M, Mao J, Rowley JD, Bohlander SK . The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3-clathrin assembly protein family Proc Natl Acad Sci USA 1996 93: 4804–4809
Chaplin T, Bernard O, Beverloo HB, Saha V, Hagemeijer A, Berger R, Young BD . The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene Blood 1995 86: 2073–2076
Chaplin T, Ayton P, Bernard OA, Saha V, Della Valle V, Hillion J, Gregorini A, Lillington D, Berger R, Young BD . A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia Blood 1995 85: 1435–1441
Beverloo HB, Le Coniat M, Wijsman J, Lillington DM, Bernard O, de Klein A, van Wering E, Welborn J, Young BD, Hagemeijer A, Berger R . Breakpoint heterogeneity in t(10;11) translocation in AML-M4/M5 resulting in fusion of AF10 and MLL is resolved by fluorescent in situ hybridization analysis Cancer Res 1995 55: 4220–4224
Tanabe S, Bohlander SK, Vignon CV, Espinosa R, Zhao N, Strissel PL, Zeleznik-Le N, Rowley JD . AF10 is split by MLL and HEAB, a human homolog to a putative Caenorhabditis elegans ATP/GTP-binding protein in an invins (10;11)(p12;q23q12) Blood 1996 88: 3535–3545
Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y . Hematologic malignancies with the t(10;11)(p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes Genes Chromosomes Cancer 1997 20: 253–259
Dreyling MH, Schrader K, Fonatsch C, Schlegelberger B, Haase D, Schoch C, Ludwig W-D, Löffler H, Büchner T, Wörmann B, Hiddemann W, Bohlander SK . MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis Blood 1998 91: 4662–4667
Hiddemann W, Heinecke A, Büchner T . Results of the German AML cooperative group. Büchner T, Hiddemann W, Wörmann B (eds). In: Haematology and Blood Transfusion: Acute Leukemias VI Springer: Berlin 1997 p 769
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC . A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group Blood 1994 84: 1361–1392
Bennett JM, Catovsky C, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . Proposals for the classification of the acute leukemias Br J Haematol 1976 33: 451–458
Rothe G, Schmitz G, Adorf D, Barlage S, Gramatzki M, Hanenberg H, Höffkes HG, Janossy G, Knüchel R, Ludwig WD, Nebe T, Nerl C, Orfao A, Serke S, Sonnen R, Tichelli A, Wörmann B . Consensus protocol for the flow cytometric immunophenotyping of hematopoietic malignancies Leukemia 1996 10: 877–895
Nisson PE, Rashtchian A, Watkins PC . Rapid and efficient cloning of Alu-PCR products using uracil DNA glycosylase PCR Meth Appl 1991 1: 120–123
Carlson KM, Bohlander SK, Vignon C, Martinez-Climent JA, Le Beau MM, Rowley JD . Identification and molecular characterization of CALM/AF10 fusion products in acute lymphoblastic leukemia and acute myeloid leukemia Leukemia 1999 (submitted)
Silliman CC, McGavran L, Wei Q, Miller LA, Li S, Hunger SP . Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-p14;q14–q21) suggests a potential role for truncated AF10 polypeptides Leukemia 1998 12: 1404–1410
Kumon K, Kobayashi H, Maseki N, Sakashita A, Sakurai M, Tanizawa A, Imashuku S, Kaneko Y . Mixed-lineage leukemia with t(10;11)(p13;q21): an analysis of AF10-CALM and CALM-AF10 fusion mRNAs and clinical features Genes Chromosomes Cancer 1999 25: 33–39
Saha V, Chaplin T, Gregorini A, Ayton P, Young BD . The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins Proc Natl Acad Sci USA 1995 92: 9737–9741
Linder B, Jones LK, Chaplin T, Mohd-Sarip A, Heinlein UA, Young BD, Saha V . Expression pattern and cellular distribution of the murine homologue of AF10 Biochim Biophys Acta 1998 1443: 285–296
Tebar F, Bohlander SK, Sorkin A . Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic coated pits, interactions with clathrin and the impact of overexpression on clathrin-mediated traffic Mol Cell Biol 1999 10: 2687–2702
Sundstrom C, Nilsson K . Establishment and characterization of a human histiocytic lymphoma cell line (U937) Int J Cancer 1976 17: 565–577
Narita M, Shimizu K, Hayashi Y, Taki T, Taniwaki M, Hosoda F, Kobayashi H, Nakamura H, Sadamori N, Ohnishi H, Bessho J, Yanagisawa M, Ohki M . Consistent detection of CALM-AF10 chimaeric transcripts in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts Br J Haematol 1999 105: 928–937
Acknowledgements
We would like to thank Dr JD Rowley and Dr K Carlson for critically reading this manuscript and sharing prepublication data with us.
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Bohlander, S., Muschinsky, V., Schrader, K. et al. Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients. Leukemia 14, 93–99 (2000). https://doi.org/10.1038/sj.leu.2401614
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DOI: https://doi.org/10.1038/sj.leu.2401614
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