|Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation.|
|PMID: 9680349 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.|
|Title: Blood Volume: 92 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 1998 Aug|
|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|
|Languages: eng Pagination: 810-21 Citation Subset: AIM; IM|
|Copyright 1998 by The American Society of Hematology.|
|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.|
|APA/MLA Format Download EndNote Download BibTex|
Antineoplastic Combined Chemotherapy Protocols
Bone Marrow / pathology
Bone Marrow Transplantation
Cell Transformation, Neoplastic / genetics
Chromosomes, Human, Pair 11 / genetics*, ultrastructure
Chromosomes, Human, Pair 4 / genetics*, ultrastructure
Combined Modality Therapy
Fetal Proteins / analysis
Gene Expression Regulation, Developmental
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells / metabolism*
Liver / embryology, pathology
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
Sensitivity and Specificity
Translocation, Genetic / genetics*
Tumor Markers, Biological / analysis*, biosynthesis, genetics
|CA-13539/CA/NCI NIH HHS; CA-60437/CA/NCI NIH HHS|
|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|
Blood. 1998 Aug 1;92(3):709-11
Blood. 1999 Feb 1;93(3):1107-8 [PMID: 10025981 ]
Blood. 1999 Feb 1;93(3):1106-7; author reply 1108-10 [PMID: 10025980 ]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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