Abstract
More than 40 genes have been reported as translocation partners of the mixed lineage leukemia gene(MLL) in hematologic malignancies.AF17 was identified earlier than most otherMLL translocation partners. On the other hand, there is only 1 report of anMLL- AF17 fusion transcript in acute myeloid leukemia (AML). Here we describe a 40-year-old man with a diagnosis of AML involving t(11;17)(q23;q21). We identified a chromosomal breakpoint for t(11;17)(q23;q21) atMLL intron 6 andAF17 intron 8. Although the previously reported form of theMLL- AF17 fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (PCR) analysis, a novel form of anMLL- AF17 fusion transcript joiningMLL exon 6 toAF17 exon 9 was detected by complementary DNA panhandle PCR. The fact that 2 forms ofMLL- AF17 retain the leucine zipper domain ofAF17 suggests that the dimerization domain ofAF17 is critical for leukemogenesis by theMLL- A F17 fusion gene.
Similar content being viewed by others
References
Redner RL. Variations on a theme: the alternate translocations in APL.Leukemia. 2002;16:1927–1932.
Prasad R, Leshkowitz D, Gu Y, et al. Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia.Proc Natl Acad Sci U S A. 1994;91:8107–8111.
Strehl S, Borkhardt A, Slany R, Fuchs UE, Konig M, Haas OA. The humanLASP1 gene is fused toMLL in an acute myeloid leukemia with t(11;17)(q23;q21).Oncogene. 2003;22:157–160.
Ayton PM, Cleary ML. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins.Oncogene. 2001;20:5695–5707.
Taki T, Ohnishi H, Shinohara K, et al.AF17q25, a putative septin family gene, fuses theMLL gene in acute myeloid leukemia with t(11;17)(q23;q25).Cancer Res. 1999;59:4261–4265.
Megonigal MD, Rappaport EF, Wilson RB, et al. Panhandle PCR for cDNA: a rapid method for isolation ofMLL fusion transcripts involving unknown partner genes.Proc Natl Acad Sci U S A. 2000; 97:9597–9602.
Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y.LCX, leukemia-associated protein with a CXXC domain, is fused toMLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).Cancer Res. 2002;62:4075–4080.
Ono R, Taki T, Taketani T, et al.SEPTIN6, a human homologue to mouseSeptin6, is fused toMLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24.Cancer Res. 2002;62:333–337.
Taketani T, Taki T, Shibuya N, et al. TheHOXD11 gene is fused to theNUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15).Cancer Res. 2002;62:33–37.
Spitzner JR, Muller MT. A consensus sequence for cleavage by vertebrate DNA topoisomerase II.Nucleic Acids Res. 1988;16:5533–55566.
Martin ME, Milne TA, Bloyer S, et al. Dimerization of MLL fusion proteins immortalizes hematopoietic cells.Cancer Cell. 2003;4:197–2077.
So CW, Lin M, Ayton PM, Chen EH, Cleary ML. Dimerization contributes to oncogenic activation of MLL chimeras in acute leukemias.Cancer Cell. 2003;4:99–110.
Cin PD, Sherman L, Marzelli M, McLaughlin C, Zukerberg L, Amrein PC. A new case of t(11;17)(q23;q21) withMLL rearrangement.Cancer Genet Cytogenet. 2004;148:178–179.
Dube S, Fetni R, Hazourli S, Champagne M, Lemieux N. Rearrangement of theMLL gene and a region proximal to theRARα gene in a case of acute myelocytic leukemia M5 with a t(11; 17)(q23;q21).Cancer Genet Cytogenet. 2003;145:54–59.
Reeves BR, Kempski H, Jani K, et al. A case of acute monocytic leukemia with t(11;17) involving a rearrangement of MLL-1 and a region proximal to the RARA gene.Cancer Genet Cytogenet. 1994;74:50–53.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Suzukawa, K., Shimizu, S., Nemoto, N. et al. Identification of a Chromosomal Breakpoint and Detection of a Novel Form of an MLL- AF17 Fusion Transcript in Acute Monocytic Leukemia with t(11;17)(q23;q21). Int J Hematol 82, 38–41 (2005). https://doi.org/10.1532/IJH97.05025
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1532/IJH97.05025