Document Detail


MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.
MedLine Citation:
PMID:  9616163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The translocation t(10;11)(p13;q14) has been observed in acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). A recent study showed a MLL/AF10 fusion in all cases of AML with t(10;11) and various breakpoints on chromosome 11 ranging from q13 to q23. We recently cloned CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the monocytic cell line U937. To further define the role of these genes in acute leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology, immunophenotype, and clinical course were analyzed. Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region, and a YAC spanning the AF10 breakpoint. Rearrangement of at least one of these genes was detected in all cases with balanced t(10;11). In 4 cases, including 3 AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of the CALM YACS were separated in interphase cells, indicating a translocation breakpoint within the CALM region. MLL was rearranged in 3 AML with myelomonocytic differentiation (2 AML-M2 and 1 AML-M5), including 1 secondary AML. In all 3 cases, a characteristic immunophenotype was identified (CD4+, CD13-, CD33+, CD65s+). AF-10 was involved in 5 of 6 evaluable cases, including 1 case without detectable CALM or MLL rearrangement. In 2 complex translocations, none of the three genes was rearranged. All cases had a remarkably poor prognosis, with a mean survival of 9.6 +/- 6.6 months. For the 7 AML cases that were uniformly treated according to the AMLCG86/92 protocols, disease-free and overall survival was significantly worse than for the overall study group (P = .03 and P = .01, respectively). We conclude that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis.
Authors:
M H Dreyling; K Schrader; C Fonatsch; B Schlegelberger; D Haase; C Schoch; W Ludwig; H Löffler; T Büchner; B Wörmann; W Hiddemann; S K Bohlander
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Blood     Volume:  91     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-06-30     Completed Date:  1998-06-30     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4662-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Hematology/Oncology, University of Göttingen, Göttingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Aged
Child, Preschool
Chromosomes, Human, Pair 10*
Chromosomes, Human, Pair 11*
Clathrin / genetics*
DNA-Binding Proteins / genetics*
Female
Gene Rearrangement
Humans
Leukemia / genetics*,  pathology,  physiopathology
Lymphocyte Subsets / pathology
Male
Middle Aged
Myeloid-Lymphoid Leukemia Protein
Prognosis
Proto-Oncogenes*
Transcription Factors / genetics*
Translocation, Genetic*
Chemical
Reg. No./Substance:
0/Clathrin; 0/DNA-Binding Proteins; 0/MLL protein, human; 0/MLLT10 protein, human; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein

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