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Molecular analysis of single colonies reveals a diverse origin of initial clonal proliferation in B-precursor acute lymphoblastic leukemia that can precede the t(12;21) translocation.
Cancer Res. 2001 Dec 01; 61(23):8547-53.CR

Abstract

The pathogenesis of pediatric B-precursor acute lymphoblastic leukemia is largely unknown, and even with nonrandom chromosomal translocations present, the precise order of clonal molecular events is undefined. We developed an in vitro system using cytokines interleukin (IL)-3, IL-7, IL-10, and FMS-like tyrosine kinase 3 ligand with CD40 ligand-expressing fibroblasts to obtain single blast colonies from which clonal immunoglobulin heavy chain (IgH), T-cell receptor delta gene rearrangements, and, in t(12;21)-positive cases, TEL-AML1 fusion transcripts could be simultaneously PCR amplified. The proliferation of early tumor progenitors increased subclone detection enabling us, in seven diagnostic samples, to determine the stage of differentiation at which each leukemia occurred. Four were derived from the stage before initiation of IgH rearrangement, one during recombination of variable, joining, and diversity segments of the heavy chain gene VDJ(H), and two after completion of IgH rearrangement. Furthermore, analysis of a t(12;21)-positive leukemia with unusually late onset, identified both TEL-AML1-positive and -negative colonies carrying a clonal T-cell receptor delta rearrangement, inferring the presence of clonal expansion before the occurrence of the t(12;21). In contrast, in a typical, early onset t(12;21)-positive leukemia, the t(12;21) appeared to be the first clonal event. In both leukemias, the t(12;21) occurred before recombination of variable, joining and diversity segments of the heavy chain gene VDJ.

Authors+Show Affiliations

CRC Institute for Cancer Studies, University of Birmingham, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11731441

Citation

Weston, V J., et al. "Molecular Analysis of Single Colonies Reveals a Diverse Origin of Initial Clonal Proliferation in B-precursor Acute Lymphoblastic Leukemia That Can Precede the T(12;21) Translocation." Cancer Research, vol. 61, no. 23, 2001, pp. 8547-53.
Weston VJ, McConville CM, Mann JR, et al. Molecular analysis of single colonies reveals a diverse origin of initial clonal proliferation in B-precursor acute lymphoblastic leukemia that can precede the t(12;21) translocation. Cancer Res. 2001;61(23):8547-53.
Weston, V. J., McConville, C. M., Mann, J. R., Darbyshire, P. J., Lawson, S., Gordon, J., Moss, P. A., Taylor, A. M., & Stankovic, T. (2001). Molecular analysis of single colonies reveals a diverse origin of initial clonal proliferation in B-precursor acute lymphoblastic leukemia that can precede the t(12;21) translocation. Cancer Research, 61(23), 8547-53.
Weston VJ, et al. Molecular Analysis of Single Colonies Reveals a Diverse Origin of Initial Clonal Proliferation in B-precursor Acute Lymphoblastic Leukemia That Can Precede the T(12;21) Translocation. Cancer Res. 2001 Dec 1;61(23):8547-53. PubMed PMID: 11731441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis of single colonies reveals a diverse origin of initial clonal proliferation in B-precursor acute lymphoblastic leukemia that can precede the t(12;21) translocation. AU - Weston,V J, AU - McConville,C M, AU - Mann,J R, AU - Darbyshire,P J, AU - Lawson,S, AU - Gordon,J, AU - Moss,P A, AU - Taylor,A M, AU - Stankovic,T, PY - 2001/12/4/pubmed PY - 2002/1/5/medline PY - 2001/12/4/entrez SP - 8547 EP - 53 JF - Cancer research JO - Cancer Res VL - 61 IS - 23 N2 - The pathogenesis of pediatric B-precursor acute lymphoblastic leukemia is largely unknown, and even with nonrandom chromosomal translocations present, the precise order of clonal molecular events is undefined. We developed an in vitro system using cytokines interleukin (IL)-3, IL-7, IL-10, and FMS-like tyrosine kinase 3 ligand with CD40 ligand-expressing fibroblasts to obtain single blast colonies from which clonal immunoglobulin heavy chain (IgH), T-cell receptor delta gene rearrangements, and, in t(12;21)-positive cases, TEL-AML1 fusion transcripts could be simultaneously PCR amplified. The proliferation of early tumor progenitors increased subclone detection enabling us, in seven diagnostic samples, to determine the stage of differentiation at which each leukemia occurred. Four were derived from the stage before initiation of IgH rearrangement, one during recombination of variable, joining, and diversity segments of the heavy chain gene VDJ(H), and two after completion of IgH rearrangement. Furthermore, analysis of a t(12;21)-positive leukemia with unusually late onset, identified both TEL-AML1-positive and -negative colonies carrying a clonal T-cell receptor delta rearrangement, inferring the presence of clonal expansion before the occurrence of the t(12;21). In contrast, in a typical, early onset t(12;21)-positive leukemia, the t(12;21) appeared to be the first clonal event. In both leukemias, the t(12;21) occurred before recombination of variable, joining and diversity segments of the heavy chain gene VDJ. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11731441/Molecular_analysis_of_single_colonies_reveals_a_diverse_origin_of_initial_clonal_proliferation_in_B_precursor_acute_lymphoblastic_leukemia_that_can_precede_the_t_12 L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11731441 DB - PRIME DP - Unbound Medicine ER -