Induction of granulocytic differentiation by 2 pathways

Zhang, Pu; Nelson, Erik A.; Radomska, Hanna S.; Iwasaki-Arai, Junko; Akashi, Koichi; Friedman, Alan D.; Tenen, Daniel G.

doi:10.1182/blood.v99.12.4406

Cited by 67 publications

(49 citation statements)

References 38 publications

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“…And defects in the respiratory burst response were only observed in neutrophils from hck Ϫ/Ϫ / fgr Ϫ/Ϫ /lyn Ϫ/Ϫ triple knockout mice (47). Since myeloid development can be regulated by multiple pathways (1,48), it is likely that in addition to Fer there may be other mechanisms capable of compensating for the absence of Fes. For these reasons, we believe that both loss-and gain-of-function genetic approaches will be required to elucidate the biological functions and mechanism of action of Fes.…”

Section: Discussionmentioning

confidence: 99%

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors

Kim

Ogata

Feldman

2003

Journal of Biological Chemistry

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The c-fps/fes proto-oncogene encodes a 92-kDa protein-tyrosine kinase that is involved in myeloid cell development and function. We have recently shown that expression of an activated allele of Fes (Fes act ) in monocyte precursors resulted in their differentiation into functional macrophages through the activation of lineage-specific transcription factors. We now report that this kinase also plays a role in the survival and terminal differentiation of granulocyte progenitors. The expression of Fes act in factor-dependent 32D cells prevented their apoptotic death after interleukin-3 removal, but Fes act -expressing cells remained factor-dependent for proliferation. Removal of interleukin-3 from the Fes actexpressing cells was followed by granulocytic differentiation in the absence of granulocyte colony-stimulating factor within 4 -8 days. The differentiated cells had distinctive granulocyte morphology and there was up-regulation of CD11b, Gr-1, and late differentiation markers such as lactoferrin, suggesting that this kinase induced terminal granulocytic differentiation. Concomitantly, Fes act down-regulated the macrophage marker F4/80, suggesting that the biological activity of Fes was coordinated in a lineage-specific manner. Further analysis showed that Fes act caused activation of CCAAT/enhancer-binding protein-␣ and STAT3, two transcription factors that are involved in granulocyte differentiation. Our results provide evidence that Fes may be a key component of the granulocyte differentiation machinery, and suggest a potential mechanism by which this kinase may regulate granulocyte-specific gene expression.

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Section: Discussionmentioning

confidence: 99%

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors

Kim

Ogata

Feldman

2003

Journal of Biological Chemistry

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“…[24][25][26] MPO represents an early-appearing and highly reliable intracellular myeloid lineage marker, [27][28][29] which is detected in a subset of human hematopoietic bone marrow progenitor cells and in granulomonocytic cells. 30 Cathepsin G is highly expressed at the promyelocytic stage of myeloid development and also functions to stimulate the proliferation of lymphocytes.…”

Section: Decreased Expression Of Myeloid-specific Genes In Cited2 ؊/؊mentioning

confidence: 99%

Cited2 is required for normal hematopoiesis in the murine fetal liver

Chen¹,

Haviernik

Bunting

et al. 2007

Blood

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“…In hematopoiesis, CEBPA plays a pivotal role in early stages of myeloid differentiation and is particularly expressed in myelomonocytic cells. [4][5][6][7][8] CEBPA has multiple actions such as downregulation of C-MYC expression allowing differentiation, direct upregulation of the expression of granulocytic lineage-specific genes and synergistic action with other key genes in myeloid development including CBF complex genes and PU.1. 5,9-11 In addition to specific DNA binding, CEBPA could act by proteinprotein interaction.…”

Section: Introductionmentioning

confidence: 99%

CEBPA point mutations in hematological malignancies

et al. 2005

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The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcription factor strongly implicated in myelopoiesis through control of proliferation and differentiation of myeloid progenitors. Recently, several works have reported the presence of CEBPA-acquired mutations in hematological malignancies. In this work, we analyzed characteristics of mutations and their correlation with disease characteristics described in previous studies. In the 1175 patients reported, 146 CEBPA mutations were identified in 96 patients. Mutations were found in the whole gene sequence, but cluster regions were clearly identified. Furthermore, two categories of mutations were reported: out-of-frame ins/del often in the N-terminal region, and in-frame ins/del often in the C-terminal region. CEBPA mutations were reported exclusively in acute myeloid leukemia (AML) (according to WHO classification criteria) and mutated patients preferentially belonged to M1, M2 and M4 FAB subtypes. All but one case belonged to the 'intermediate' prognostic subgroup of MRC classification. In the absence of poor prognostic factors, patients with CEBPA mutation had favorable outcome, very similar to that of the t(8;21), inv(16), t(15;17) subgroup. Systematic analysis of CEBPA mutations, in addition to that of alterations in master genes of hematopoiesis, may be useful to assess the prognosis of AML particularly in patients belonging to the 'intermediate' prognostic subgroup.

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Induction of granulocytic differentiation by 2 pathways

Cited by 67 publications

References 38 publications

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors

Cited2 is required for normal hematopoiesis in the murine fetal liver

CEBPA point mutations in hematological malignancies

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