Abstract
The t(10;11)(p12-p13;q14-q21) observed in a subset of patients with either acute lymphoblastic leukemia or acute myeloid leukemia has been shown to result in the fusion of AF10 on chromosome 10 with CALM (also named CLTH) on chromosome 11. AF10 was originally identified as a fusion partner of MLL in the t(10;11)(p12-p13;q23) observed in myeloid leukemia. CALM is a newly isolated gene, cloned as the fusion partner of AF10 in the monocytoid cell line, U937. In order to understand the relationship between MLL, AF10, CALM and the leukemic process, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction were used to study a series of nine leukemia patients with a t(10;11). Six had myeloid leukemia (AML-M0, AML-M1, AML-M4 and AML-M5) and three had T cell lymphoblastic leukemia. We identified four different CALM/AF10 fusion products in five patients and AF10/CALM reciprocal message in one. We conclude that fusion of CALM and AF10 is a recurring abnormality in both lymphoid and myeloid leukemias of various types including AML-M5, and that the breakpoints in the two types of leukemia do not differ. Our data indicate that the CALM/AF10 fusion product on the der(10) chromosome is critical to leukemogenesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kaneko Y, Maseki N, Takasaki N, Sakurai N, Hayashi Y, Nakazawa S, Mori T, Sakurai M, Takeda T, Shikano T, Hiyoshi Y . Clinical and hematologic characteristics in acute leukemia with 11q23 translocations Blood 1986 67: 484–491
Pui CH, Raimondi SC, Murphy SB, Ribeiro RC, Kalwinsky DK, Dahl GV, Crist WM, Williams DL . An analysis of leukemic cell chromosomal features in infants Blood 1987 69: 1289–1293
Groupe Française de Cytogenetique Hematologique . t(10;11)(p13–14;q14–21): a new recurrent translocation in T cell acute lymphoblastic leukemias Genes Chromos Cancer 1991 3: 411–415
Height SE, Dainton MG, Kearney L, Swansbury GJ, Matutes E, Dyer MJS, Treleaven JG, Powles RL, Catovsky D . Acute myelomonocytic leukemia with t(10;11)(p13;q23): heterogeneity of breakpoints at 11q23 and association with recombinase activation Genes Chromos Cancer 1994 11: 136–139
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
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 Chromos Cancer 1997 20: 253–259
Dreyling MH, Schrader K, Fonatsch C, Schlegelberger B, Haase D, Schoch C, Ludwig WD, 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
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 Chromos Cancer 1999 25: 33–39
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
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 on to the HRX gene Blood 1995 86: 2073–2076
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
Bohlander SK, Espinosa R, Fernald AA, Rowley JD, LeBeau MM, Diaz MO . Sequence-independent amplification and labeling of yeast artificial chromosomes for fluorescence in situ hybridization Cytogenet Cell Genet 1994 65: 108–110
Espinosa R, LeBeau MM . Gene mapping by FISH. In: Boultwood J (ed) Methods in Molecular Biology, Vol 68: Gene Isolation and Mapping Protocols Humana Press: Totowa, NJ 1996 pp 53–76
Bohlander SK, Muschinsky V, Schrader K, Siebert R, Schlegelberger B, Harder L, Fonatsch C, Ludwig WD, Hiddemann W, Dreyling MH . Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and non-Hodgkin's lymphoma patients Leukemia 2000 14: 93–99
Sundstrom C, Nilsson K . Establishment and characterization of a human histiocytic lymphoma cell line (U937) Int J Cancer 1976 17: 565–577
Ikushima S, Yoshihara T, Fujikawa F, Todo S, Misawa S, Nakagawa H, Yumura K, Kawa K, Morioka Y, Imashuku S . Establishment of a monocytoid cell line (KP-MO-TS) from a patient with acute monocytic leukemia and a mediastinal mass Acta Haematol Jpn 1990 53: 678–687
Super HJ, McCabe NR, Thirman MJ, Larson RA, Le Beau MM, Pedersen-Bjergaard J, Philip P, Diaz MO, Rowley JD . Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II Blood 1993 82: 3705–3711
Tanabe S, Bohlander S, 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
Acknowledgements
We are grateful to Marjorie Isaacson for retrieval of patient information and data management, and to Dr Carlos Suarez, Loyola University Medical Center, for referral of patient 5. This work was supported in part by the National Cancer Institute, CA 42557 (JDR). KC was supported by the G Harold and Leila Y Mathers Charitable Foundation.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carlson, K., Vignon, C., Bohlander, S. et al. Identification and molecular characterization of CALM/AF10fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia. Leukemia 14, 100–104 (2000). https://doi.org/10.1038/sj.leu.2401629
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401629
Keywords
This article is cited by
-
Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells
Clinical and Translational Oncology (2021)
-
The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models
Leukemia (2016)
-
HOX-mediated LMO2 expression in embryonic mesoderm is recapitulated in acute leukaemias
Oncogene (2013)
-
The clathrin-binding domain of CALM-AF10 alters the phenotype of myeloid neoplasms in mice
Oncogene (2012)
-
CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12
Leukemia (2012)