Abstract
We determined bone marrow karyotype at diagnosis in four female acute myeloid leukemia (AML) or myelodysplasia patients, aged between 52 and 56 years. In each case, we observed chromosome rearrangement involving the same 4q24 band. Three patients had a balanced reciprocal translocation as the sole abnormality – t(3;4)(q26;q24), t(4;5)(q24;p16) and t(4;7)(q24;q21) – and the fourth had del(4)(q23q24), +4. We used a set of 4q BAC probes for fluorescent in situ hybridization (FISH) in these four cases. We found a 4q24 submicroscopic deletion in all three translocations, with a common deletion of approximately 0.5 Mb. In three cases, we concluded that rearrangement occurred in an early hematopoietic stem cell, as it was detected, in mosaic with a normal karyotype, in a fraction of remission bone marrow cells, peripheral T and B lymphocytes, malignant lymph node T-lymphoma cells in one case and B-lymphoblastoid cell lines established in two cases. Moreover, one of 10 additional AML patients tested by FISH had a normal karyotype and deletion of one of the commonly deleted probe sequences. A tumor suppressor gene may therefore be involved, especially as two patients developed malignant lymphoma at the same time as myeloid proliferation.
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References
Mitelman F, Johansson B, Mertens F . Mitelman database of chromosome aberrations in cancer 2001. http://cgap.nci.nih.gov/Chromosomes/Mitelman.
Mrozek K, Heerema NA, Bloomfield CD . Cytogenetics in acute leukemia. Blood Rev 2004; 18: 115–136.
Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D et al. Involvement and functional impairment of the CD34(+)CD38(−)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 2002; 100: 259–267.
Fialkow PJ, Singer JW, Adamson JW, Vaidya K, Dow LW, Ochs J et al. Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. Blood 1981; 57: 1068–1073.
Ferraris AM, Broccia G, Meloni T, Canepa L, Sessarego M, Gaetani GF . Clonal origin of cells restricted to monocytic differentiation in acute nonlymphocytic leukemia. Blood 1984; 64: 817–820.
Heaney ML, Golde DW . Myelodysplasia. N Engl J Med 1999; 340: 1649–1660.
Janssen JW, Buschle M, Layton M, Drexler HG, Lyons J, van den Berghe H et al. Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. Blood 1989; 73: 248–254.
Tsukamoto N, Morita K, Maehara T, Okamoto K, Karasawa M, Omine M et al. Clonality in myelodysplastic syndromes: demonstration of pluripotent stem cell origin using X-linked restriction fragment length polymorphisms. Br J Haematol 1993; 83: 589–594.
Haase D, Feuring-Buske M, Konemann S, Fonatsch C, Troff C, Verbeek W et al. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood 1995; 86: 2906–2912.
Miyamoto T, Weissman IL, Akashi K . AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukaemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 2000; 97: 7521–7526.
Mitelman F (ed). ISCN. An International System for Human Cytogenetic Nomenclature. Basel: S Karger, 1995.
Maserati E, Aprilui F, Vinante F, Locatelli F, Amendola G, Zatterale A et al. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15–20% of cases. Genes Chromosomes Cancer 2002; 33: 93–97.
Bodmer D, Eleveld M, Kater-Baats E, Janssen I, Janssen B, Weterman M et al. Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). Hum Mol Genet 2002; 11: 641–649.
Yeo W, Wong N, Chow J, Tsoi WC, Johnson PJ, Wickham N . Small cell variant of Ki-1 lymphoma associated with myelofibrosis and a novel constitutional chromosomal translocation t(3;4) (q13;q12). J Clin Pathol 1996; 49: 259–262.
Daibata M, Nemoto Y, Komatsu N, Machida H, Miyoshi I, Taguchi H . Constitutional t(3;11)(p21;q23) in a family, including one member with lymphoma: establishment of novel cell lines with this translocation. Cancer Genet Cytogenet 2000; 117: 28–31.
Kitamura E, Kuemerle BA, Chernova OB, Cowell JK . Molecular characterization of the breakpoint region associated with a constitutional t(2;15)(q34;q26) in a patient with multiple myeloma. Cancer Genet Cytogenet 2001; 129: 112–119.
Lafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y et al. Detection of large-scale variation in the human genome. Nat Genet 2004; 36: 949–951.
Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P et al. Large-scale copy number polymorphism in the human genome. Science 2004; 305: 525–528.
Huntly BJ, Bench A, Green AR . Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia. Blood 2003; 102: 1160–1168.
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.
Christensen K, Kristiansen M, Hagen-Larsen H, Skytthe A, Bathum L, Jeune B et al. X-linked genetic factors regulate hematopoietic stem-cell kinetics in females. Blood 2000; 95: 2449–2451.
Cools J, Stover EH, Wlodarska I, Marynen P, Gilliland DG . The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Curr Opin Hematol 2004; 11: 51–57.
Acknowledgements
We thank M Rocchi and P de Jong for kindly supplying us with BAC probes. We also thank Cochin Hospital Cell Bank (Dr D Recan) for establishing lymphoblastoid cell lines and Fanny Couturier and Nathalie Koehler for excellent technical assistance. This study was supported in part by funds from the Comité de Paris de la Ligue Nationale Contre le Cancer.
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Viguié, F., Aboura, A., Bouscary, D. et al. Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?. Leukemia 19, 1411–1415 (2005). https://doi.org/10.1038/sj.leu.2403818
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DOI: https://doi.org/10.1038/sj.leu.2403818
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