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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice

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Lange, A. P. [1, 2] ; Almeida, L. Y. [1, 2] ; Araujo Silva, C. L. [1, 2] ; Scheucher, P. S. [1, 2] ; Chahud, F. [3] ; Krause, A. [4] ; Bohlander, S. K. [5] ; Rego, E. M. [1, 2, 6]
Total Authors: 8
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Div Hematol, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ctr Terapia Celular, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol & Med Legal, Ribeirao Preto, SP - Brazil
[4] Univ Fed Santa Maria, Lab Anal Clin Vet, Santa Maria, RS - Brazil
[5] Univ Auckland, Dept Mol Med & Pathol, Leukaemia & Blood Canc Res Unit, Auckland - New Zealand
[6] Univ Sao Paulo, Fac Med, Div Hematol, LIM31, Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 52, n. 6 2019.
Web of Science Citations: 0

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1(+)/B220(+)/c-Kit(+ )cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential. (AU)

FAPESP's process: 11/17111-4 - In vivo study of the role of CCAAT Enhancer Binding Protein alpha (CEBPA)gene hipoexpression in the leukemogenesis induced by the CALM/AF10 hybrid protein
Grantee:Ana Paula Alencar de Lima Lange
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/02713-2 - Effects of erlotinib and gefitinib therapy in combination with all-trans retinoic acid and arsenic trioxide in Acute Promyelocytic Leukemia: in vitro, ex vivo and murine experimental model studies
Grantee:Luciana Yamamoto de Almeida
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC