Document Detail


Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation.
MedLine Citation:
PMID:  9680349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leukemic cells from bone marrow (BM) of 17 infants and 127 children with newly diagnosed ALL, as well as fetal liver and BM and normal infant BM samples, were analyzed for presence of a t(4;11) translocation using standard cytogenetic techniques and expression of an MLL-AF4 fusion transcript using standard reverse transcriptase-polymerase chain reaction (RT-PCR) assays as well as nested RT-PCR that is 100-fold more sensitive than standard RT-PCR. Overall, 9 of 17 infants and 17 of 127 noninfant pediatric ALL patients were positive for expression of MLL-AF4 fusion transcripts, as determined by standard and/or nested RT-PCR assays. None of the MLL-AF4(+) cases were positive for E2A-PBX1 or BCR-ABL fusion transcript expression. Although 8 of 9 MLL-AF4(+) infants had cytogenetically detectable t(4;11)(q21;q23), 15 of the 17 MLL-AF4(+) noninfants were t(4;11)-. Infants with MLL-AF4(+) ALL had poor outcomes, whereas non-infant MLL-AF4(+)/t(4;11)- patients had favorable outcomes similar to MLL-AF4(-) patients. Notably, MLL-AF4 transcripts also were detected by nested RT-PCR in 4 of 16 fetal BMs, 5 of 13 fetal livers, and 1 of 6 normal infant BMs, but not in any of the 44 remission BM specimens from pediatric ALL patients. Our results provide unprecedented evidence that MLL-AF4 fusion transcripts can be present in normal hematopoietic cells, indicating that their expression is insufficient for leukemic transformation of normal lymphocyte precursors.
Authors:
F M Uckun; K Herman-Hatten; M L Crotty; M G Sensel; H N Sather; L Tuel-Ahlgren; M B Sarquis; B Bostrom; J B Nachman; P G Steinherz; P S Gaynon; N Heerema
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  92     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-08-27     Completed Date:  1998-08-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  810-21     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 1998 by The American Society of Hematology.
Affiliation:
Children's Cancer Group ALL Biology Reference Laboratory, Parker Hughes Cancer Center, and the Departments of Biology, Immunology, and Molecular Genetics, Hughes Institute, St Paul, MN, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Bone Marrow / pathology
Bone Marrow Transplantation
Cell Transformation, Neoplastic / genetics
Child
Child, Preschool
Chromosomes, Human, Pair 11 / genetics*,  ultrastructure
Chromosomes, Human, Pair 4 / genetics*,  ultrastructure
Combined Modality Therapy
Disease-Free Survival
Female
Fetal Proteins / analysis
Gene Expression Regulation, Developmental
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells / metabolism*
Humans
Infant
Liver / embryology,  pathology
Male
Myeloid-Lymphoid Leukemia Protein
Neoplasm Proteins / analysis*,  biosynthesis,  genetics
Neoplastic Stem Cells / metabolism*
Oncogene Proteins, Fusion / biosynthesis,  genetics*
Polymerase Chain Reaction / methods
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  mortality,  pathology,  therapy
Prognosis
Remission Induction
Sensitivity and Specificity
Survival Analysis
Translocation, Genetic / genetics*
Treatment Outcome
Tumor Markers, Biological / analysis*,  biosynthesis,  genetics
Grant Support
ID/Acronym/Agency:
CA-13539/CA/NCI NIH HHS; CA-60437/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Fetal Proteins; 0/MLL-AF4 fusion protein, human; 0/Neoplasm Proteins; 0/Oncogene Proteins, Fusion; 0/Tumor Markers, Biological; 149025-06-9/Myeloid-Lymphoid Leukemia Protein
Comments/Corrections
Comment In:
Blood. 1998 Aug 1;92(3):709-11   [PMID:  9680337 ]
Blood. 1999 Feb 1;93(3):1107-8   [PMID:  10025981 ]
Blood. 1999 Feb 1;93(3):1106-7; author reply 1108-10   [PMID:  10025980 ]

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