| In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype. | |
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MedLine Citation:
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PMID: 14712291 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acute lymphoblastic leukemia (ALL) in infants under 1 year is strongly associated with translocations involving 11q23 (MLL gene), CD10-negative B-lineage (proB) immunophenotype, and poor outcome. The present study analyses the relationship between age, MLL rearrangements, proB-lineage, and in vitro drug resistance determined using the MTT assay. Compared to 425 children aged over 1 year with common/preB (c/preB) ALL, the 44 infants were highly resistant to steroids (for prednisolone (PRED) more than 580-fold, P=0.001) and L-asparaginase (L-ASP) (12-fold, P=0.001), but more sensitive to cytarabine (AraC) (1.9-fold, P=0.001) and 2-chlorodeoxyadenosine (2-CdA) (1.7-fold, P<0.001). No differences were found for vincristine, anthracyclines, thiopurines, epipodophyllotoxines, or 4-hydroperoxy (HOO)-ifosfamide. ProB ALL of all ages had a profile similar to infant ALL when compared with the group of c/preB ALL: relatively more resistant to L-ASP and PRED (and in addition thiopurines), and more sensitive to AraC and 2-CdA. Age was not related to cellular drug resistance within the proB ALL group (<1 year, n=32, vs >/=1 year, n=19), nor within the MLL-rearranged ALL (<1 year, n=34, vs >/=1 year, n=8). The translocation t(4;11)(q21;q23)-positive ALL cases were more resistant to PRED (>7.4-fold, P=0.033) and 4-HOO-ifosfamide (4.4-fold, P=0.006) than those with other 11q23 abnormalities. The expression of P-glycoprotein, multidrug-resistance protein, and lung-resistance protein (LRP) was not higher in infants compared to older c/preB ALL patients, but LRP was higher in proB ALL and MLL-rearranged ALL of all ages. In conclusion, infants with ALL appear to have a distinct in vitro resistance profile with the proB immunophenotype being of importance. The role of MLL cannot be excluded, with the t(4;11) being of special significance, while age appears to play a smaller role. |
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Authors:
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N L Ramakers-van Woerden; H B Beverloo; A J P Veerman; B M Camitta; A H Loonen; E R van Wering; R M Slater; J Harbott; M L den Boer; W D Ludwig; O A Haas; G E Janka-Schaub; R Pieters |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Leukemia Volume: 18 ISSN: 0887-6924 ISO Abbreviation: Leukemia Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-02-24 Completed Date: 2004-03-24 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 521-9 Citation Subset: IM |
Affiliation:
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VU University Medical Center, Department of Pediatric Hematology/Oncology, Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Distribution Antineoplastic Agents / pharmacology* DNA-Binding Proteins / genetics* Drug Resistance, Neoplasm* Drug Screening Assays, Antitumor Female Gene Rearrangement* Humans Immunophenotyping* Infant Infant, Newborn Male Myeloid-Lymphoid Leukemia Protein Neoplasm Proteins / metabolism P-Glycoprotein / metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*, genetics, pathology Proto-Oncogenes* Transcription Factors* Vault Ribonucleoprotein Particles / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA 32053/CA/NCI NIH HHS; CA29139/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/DNA-Binding Proteins; 0/MLL protein, human; 0/Neoplasm Proteins; 0/P-Glycoprotein; 0/Transcription Factors; 0/Vault Ribonucleoprotein Particles; 0/major vault protein; 149025-06-9/Myeloid-Lymphoid Leukemia Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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