| Autor: |
Sheryl M. Gough, Liat Goldberg, Marbin Pineda, Robert L. Walker, Yuelin J. Zhu, Sven Bilke, Yang Jo Chung, Joseph Dufraine, Subhadip Kundu, Elad Jacoby, Terry J. Fry, Susanna Fischer, Renate Panzer-Grümayer, Paul S. Meltzer, Peter D. Aplan |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Blood Advances, Vol 1, Iss 20, Pp 1749-1759 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2473-9529 |
| DOI: |
10.1182/bloodadvances.2017009837 |
| Popis: |
Abstract: B-1 and B-2 lymphocytes are derived from distinct developmental pathways and represent layered arms of the innate and adaptive immune systems, respectively. In contrast to a majority of murine B-cell malignancies, which stain positive with the B220 antibody, we discovered a novel form of B-cell leukemia in NUP98-PHF23 (NP23) transgenic mice. The immunophenotype (Lin− B220− CD19+ AA4.1+) was identical to that of progenitor (pro) B-1 cells, and VH gene usage was skewed toward 3′ V regions, similar to murine fetal liver B cells. Moreover, the gene expression profile of these leukemias was most similar to that of fetal liver pro-B fraction BC, a known source of B-1 B cells, further supporting a pro–B-1 origin of these leukemias. The NP23 pro–B-1 acute lymphoblastic leukemias (ALLs) acquired spontaneous mutations in both Bcor and Janus kinase (Jak) pathway (Jak1/2/3 and Stat5a) genes, supporting a hypothesis that mutations in 3 critical pathways (stem-cell self-renewal, B-cell differentiation, and cytokine signaling) collaborate to induce B-cell precursor (BCP) ALL. Finally, the thymic stromal lymphopoietin (Tslp) cytokine is required for murine B-1 development, and chromosomal rearrangements resulting in overexpression of the TSLP receptor (CRLF2) are present in some patients with high-risk BCP-ALL (referred to as CRLF2r ALL). Gene expression profiles of NP23 pro–B-1 ALL were more similar to that of CRLF2r ALL than non-CRLF2r ALL, and analysis of VH gene usage from patients with CRLF2r ALL demonstrated preferential usage of VH regions used by human B-1 B cells, leading to the suggestion that this subset of patients with BCP-ALL has a malignancy of B-1, rather than B-2, B-cell origin. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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