A t(11;12) 11q23 leukemic breakpoint that disrupts the MLL Gene

Abstract

Translocations involving 11q23 have been shown to be a consistent finding in human hematopoietic malignancies and in some constitutional abnormalities. The identification of a gene, MLL (myeloid/lymphoid or mixed-lineage leukemia), that spans the breakpoints in four different recurrent 11q23 translocations was recently reported. We describe a rare (11;12)(q23;p13) translocation, observed in leukemic cells from a patient with acute lymphoblastic leukemia, which also disrupts this gene.

Disruption of a Homolog of Trithorax by 11q23 Translocations: Leukemogenic and Transcriptional Implications

“…The HRX gene has been shown to be rearranged by 11q23 abnormalities whose reciprocal partners are located at almost 30 cytogenetically diverse loci including Ip32, lq32, lq21, 2p21, 3q23-25,4q21, 5q31, 6pI2,6q27, 7p15, 7p22, 9pl1,9p22, lOp 11-13, lOq22, 11q13, 12p13, 15q15, 16p13, 17q21, 17q25, 18q21, 19p13.l, 19p13.3, 22q12, and Xq13 (Gu et al 1992b;KEARNEY et al 1992;TKACHUK et al 1992;CORRAL et al 1993;HUNGER et al 1993;LIDA et al 1993b;JANI SAIT et al 1993;KOBAYASHI et al 1993;MORRISEY et al 1993;NAKAMURA et al 1993;PRASAD et al 1993PRASAD et al , 1994THIRMAN et al 1993aTHIRMAN et al , 1994BERNARD et al 1994;HEIGHT et al 1994;LEBLANC et al 1994;MCCABE et al 1994;PARRY et al 1994;RUBNITZ et al 1994a;SORENSEN et al 1994;CHAPLIN et al 1995a, b;FELIX et al 1995;HERNANDEZ et al 1995;MITANI et al 1995;TSE et al 1995). Notably, this degree of promiscuity is unprecedented among nonrecombinatorial genes and suggests that the breakpoint cluster region of HRX may be a recombination "hot spot" harboring highly recombinogenic sequences or structures.…”

Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities

“…[1][2][3][4] At least 40 different partner chromosomes have been involved in 11q23 translocations. [5][6][7][8][9][10][11][12] To date, 13 genes involved in translocations with MLL have been cloned. [13][14][15][16][17][18][19][20][21][22][23][24][25] It has been suggested that alteration of the MLL protein is the critical event in oncogenesis and that fusion partners may not play an important role in the oncogenic process.…”

Functional characterization of ORCTL2 ‐ an organic cation transporter expressed in the renal proximal tubules

“…The gene(s) responsible for BWS map to 11p15.5, as determined by linkage analysis of autosomal dominant pedigrees [3,4]. The complexity of the genetics of this disease is underscored by the description of distinct regions to which chromosomal breakpoints in BWS individuals have been mapped [5,6], as well as a maternal inheritance associated with familial cases suggesting a role for genomic imprinting. The identification of a number of imprinted genes at 11p15.5 has led to the postulation that disruption of imprinting (e.g.…”