Rearrangement of the MLL gene and a region proximal to the RARα gene in a case of acute myelocytic leukemia M5 with a t(11;17)(q23;q21)

Dubé, Sophie; Fetni, Raouf; Hazourli, Sawcène; Champagne, Martin A.; Lemieux, Nicole

doi:10.1016/s0165-4608(03)00056-6

Cited by 12 publications

(4 citation statements)

References 13 publications

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“…Previously, 5 cases involving MLL and a breakpoint proximal to RARA, suggesting a novel MLL partner in this region, have been described (Reeves et al, 1994;Dube et al, 2003;Classen et al, 2005;Douet-Guilbert et al, 2005;Kang et al, 2005). However, the data presented in this work and recent reports by Moore et al (2005) and Suzukawa et al (2005) provide compelling evidence that MLLT6, in accordance with the most recent genome assembly built by the Genome Bioinformatics Group of the University of California Santa Cruz (http://genome.ucsc.edu/), is physically localized proximal to RARA.…”

Section: Discussionsupporting

confidence: 58%

“…Recently, based on fluorescence in situ hybridization (FISH) data also a putative fusion between MLL and RARA has been suggested but has not been confirmed at the molecular level (Shekhter-Levin et al, 2000). Moreover, a number of cases with t(11;17) and MLL rearrangements in which the partner gene on chromosome 17 has not been identified have been reported (Reeves et al, 1994;Archimbaud et al, 1998;Harrison et al, 1998;Dube et al, 2003;Classen et al, 2005;Douet-Guilbert et al, 2005;Kang et al, 2005). In addition, another MLL fusion partner, GAS7, is located at 17p13 (Megonigal et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants

Strehl¹,

König²,

Meyer

et al. 2006

Genes Chromosomes & Cancer

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The majority of translocations that involve the long arms of chromosomes 11 and 17 in acute myeloid leukemia appear identical on the cytogenetic level. Nevertheless, they are diverse on the molecular level. At present, two genes are known in 11q23 and four in 17q12-25 that generate five distinct fusion genes: MLL-MLLT6/AF17, MLL-LASP1, MLL-ACACA or MLL-SEPT9/MSF, and ZBTB16/PLZF-RARA. We analyzed 14 cases with a t(11;17) by fluorescence in situ hybridization and molecular genetic techniques and determined the molecular characteristics of their fusion genes. We identified six different gene fusions that comprised seven cases with a MLL-MLLT6/AF17, three with a MLL-SEPT9/MSF, and one each with MLL-LASP1, MLL-ACACA, and ZBTB16/PLZF-RARA fusions. In the remaining case, a MLL-SEPT6/Xq24 fusion suggested a complex rearrangement. The MLL-MLLT6/AF17 transcripts were extremely heterogeneous and the detection of seven different in-frame transcript and splice variants enabled us to predict the protein domains relevant for leukemogenesis. The putative MLL-MLLT6 consensus chimeric protein consists of the AT-hook DNA-binding, the methyltransferase, and the CXXC zinc-finger domains of MLL and the highly conserved octapeptide and the leucine-zipper dimerization motifs of MLLT6. The MLL-SEPT9 transcripts showed a similar high degree of variability. These analyses prove that the diverse types of t(11;17)-associated fusion genes can be reliably identified and delineated with a proper combination of cytogenetic and molecular genetic techniques. The heterogeneity of transcripts encountered in cases with MLL-MLLT6/AF17 and MLL-SEPT9/MSF fusions clearly demonstrates that thorough attention has to be paid to the appropriate selection of primers to cover all these hitherto unrecognized fusion variants.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants

Strehl¹,

König²,

Meyer

et al. 2006

Genes Chromosomes & Cancer

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“…이중 4개의 MLL 결합파트너 유 전자가 17번 염색체 장완에 존재하는 것으로 보고되었는데 ALL1 fused gene from chromosome 17 (AF17 혹은 MLLT6, 17q21 에 위치), LIM and SH3 protein (LASP1 혹은 MLN50, 17q21 에 위치), MLL septin-like fusion (MSF 혹은 SEPT9, 17q25 에 위치) 및 RARA (17q21에 위치) 유전자이다 [10][11][12][13].…”

Section: 김경은•김성현•한진영unclassified

“…현재까지 APL의 변이형에서 보이는 t(11;17)(q23;q21)의 염 색체 변이를 나타내면서 형태학적으로는 APL이 아닌 AMoL으 로 진단된 증례가 전 세계적으로 7-8예 정도 보고되고 있다 [7,[10][11][12][13][14][15][16][17]. …”

Section: 김경은•김성현•한진영unclassified

Acute Monocytic Leukemia with t(11;17)(q23;q21) Involving a Rearrangement of Mixed Lineage Leukemia Gene

Kim

Han

2006

Ann Lab Med

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329A case of acute monocytic leukemia (AMoL) by French-American-British (FAB) classification in a 63-year-old male showed the abnormal karyotype 46,XY,t(11;17)(q23;q21), previously reported as a variant translocation in acute promyelocytic leukemia (APL). Fluorescence in situ hybridization (FISH) analysis identified a mixed lineage leukemia (MLL) gene rearrangement, but not visible disruptions of promyelocytic leukemia (PML) or retinoic acid receptor alpha (RARA) genes. We suggest that a certain gene proximal to RARA was rearranged in this case onto a gene close to MLL on chromosome 11q. Now, a few cases of AMoL with a similar translocation have been reported in the literature, and these cases emphasize the importance of cytogenetic and FISH studies in addition to morphology, cytochemistry, and immunophenotype in classifying acute myeloid leukemia (AML).( Korean J Lab Med 2006;26:329-33)

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AML bearing the translocation t(11;17)(q23;q21): involvement of MLL and a region close to RARA, with no differentiation response to retinoic acid

et al. 2005

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We describe a case of acute myeloid leukemia (AML) bearing the translocation t(11;17)(q23;q21). The morphological phenotype represented a monoblastic leukemia, AML French-American-British (FAB) M5a. Further analysis of the translocation revealed an involvement of the mixed-lineage leukemia (MLL) gene and a region closely proximal to the retinoic acid (RA) receptor alpha (RARA) gene. AMLs involving both a rearranged MLL and the 17q21 region, in which the RARA gene is located, have only been described in some individual cases. The functional role of this translocation is still unknown. Rearrangements of the MLL (11q23) gene in AML are usually related to the morphological phenotype FAB M5. In general, they are associated with an adverse prognosis. In acute promyelocytic leukemia, the translocation (15;17)(q22;q11-21) involving the RARA leads to a maturation arrest that can be overcome by RA, often inducing remission. In other forms of AML, however, the effects of RA are limited and diverse. To study whether RA might have a therapeutical potential in our case, we performed an in vitro analysis of RA effects on AML cells. We found that RA leads to enhanced cell death and up-regulation of CD38 and CD117. However, no hints of RA-induced in vitro differentiation were visible. Our data indicate that in AML cells bearing the t(11;17)(q23;q21), a differentiation arrest that is overcome by RA is not present. On the contrary, RA induces alterations in cellular regulation that are similar to the RA-induced changes observed in early hematogenic progenitors; thus, a possible therapeutical benefit of RA in such cases remains open.

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Rearrangement of the MLL gene and a region proximal to the RARα gene in a case of acute myelocytic leukemia M5 with a t(11;17)(q23;q21)

Cited by 12 publications

References 13 publications

Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants

Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants

Acute Monocytic Leukemia with t(11;17)(q23;q21) Involving a Rearrangement of Mixed Lineage Leukemia Gene

AML bearing the translocation t(11;17)(q23;q21): involvement of MLL and a region close to RARA, with no differentiation response to retinoic acid

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