A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein.
Genes Chromosomes Cancer
; 36(1): 26-36, 2003 Jan.
Article
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| MEDLINE
| ID: mdl-12461747
ABSTRACT
Rearrangements involving the MLL gene at chromosome band 11q23 are common in infant acute myeloid leukemias (AMLs). We recently encountered an infant patient with rapidly progressive AML whose leukemic cells harbored a previously undescribed MLL rearrangement involving an inversion of 11q [inv(11)(q14q23)]. We used panhandle PCR to determine that this rearrangement juxtaposed the MLL (Mixed-Lineage Leukemia) gene to the CALM (Clathrin Assembly Lymphoid Myeloid leukemia) gene at 11q14-q21. The CALM protein participates in recruitment of clathrin to internal membrane surfaces, thereby regulating vesicle formation in both endocytosis and intracellular protein transport. Intriguingly, CALM has been identified in other cases of AML as a translocation partner for the AF10 gene, which has independently been found to be an MLL partner in AML. We identified the MLL-CALM fusion transcript (but not the reciprocal CALM-MLL transcript) in leukemia cell RNA by RT-PCR. The predicted 1803 amino acid MLL-CALM fusion protein includes amino-terminal MLL domains involved in transcriptional repression, and carboxy-terminal CALM-derived clathrin-binding domains. The genomic breakpoint in MLL is in the 7th intron (within the breakpoint cluster region); the corresponding CALM breakpoint is in the 7th CALM intron. In contrast, breakpoints in CALM-AF10 translocations lie in the 17th-19th CALM introns (30 kb downstream); also, in these translocations, CALM provides the 5' end of the fusion transcript. Together with its previously recognized association with AF10 in AML, the identification of CALM as an MLL fusion partner suggests that interference with clathrin-mediated trafficking pathways may be an underappreciated mechanism in leukemogenesis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Cromosomas Humanos Par 11
/
Proto-Oncogenes
/
Leucemia Mieloide
/
Proteínas de Fusión Oncogénica
/
Proteínas de Ensamble de Clatrina Monoméricas
/
Proteínas de Unión al ADN
/
Inversión Cromosómica
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Infant
Idioma:
En
Revista:
Genes Chromosomes Cancer
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA