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Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia.
Nat Med. 2005 Jun; 11(6):630-7.NMed

Abstract

The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.

Authors+Show Affiliations

Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, 221 84 Lund, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

15908956

Citation

Castor, Anders, et al. "Distinct Patterns of Hematopoietic Stem Cell Involvement in Acute Lymphoblastic Leukemia." Nature Medicine, vol. 11, no. 6, 2005, pp. 630-7.
Castor A, Nilsson L, Astrand-Grundström I, et al. Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med. 2005;11(6):630-7.
Castor, A., Nilsson, L., Astrand-Grundström, I., Buitenhuis, M., Ramirez, C., Anderson, K., Strömbeck, B., Garwicz, S., Békássy, A. N., Schmiegelow, K., Lausen, B., Hokland, P., Lehmann, S., Juliusson, G., Johansson, B., & Jacobsen, S. E. (2005). Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nature Medicine, 11(6), 630-7.
Castor A, et al. Distinct Patterns of Hematopoietic Stem Cell Involvement in Acute Lymphoblastic Leukemia. Nat Med. 2005;11(6):630-7. PubMed PMID: 15908956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. AU - Castor,Anders, AU - Nilsson,Lars, AU - Astrand-Grundström,Ingbritt, AU - Buitenhuis,Miranda, AU - Ramirez,Carole, AU - Anderson,Kristina, AU - Strömbeck,Bodil, AU - Garwicz,Stanislaw, AU - Békássy,Albert N, AU - Schmiegelow,Kjeld, AU - Lausen,Birgitte, AU - Hokland,Peter, AU - Lehmann,Sören, AU - Juliusson,Gunnar, AU - Johansson,Bertil, AU - Jacobsen,Sten Eirik W, Y1 - 2005/05/22/ PY - 2004/10/19/received PY - 2005/04/26/accepted PY - 2005/5/24/pubmed PY - 2005/8/5/medline PY - 2005/5/24/entrez SP - 630 EP - 7 JF - Nature medicine JO - Nat Med VL - 11 IS - 6 N2 - The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/15908956/Distinct_patterns_of_hematopoietic_stem_cell_involvement_in_acute_lymphoblastic_leukemia_ L2 - https://doi.org/10.1038/nm1253 DB - PRIME DP - Unbound Medicine ER -