GATA1 downregulation in prefibrotic and fibrotic stages of primary myelofibrosis and in the myelofibrotic progression of other myeloproliferative neoplasms

Sangiorgio, Valentina; Nam, Anna S.; Chen, Zhengming; Orazi, Attilio

doi:10.1016/j.leukres.2020.106495

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…Compared with that in healthy controls, essential thrombocythemia or polycythemia vera, GATA1 expression level in primary myelo brosis patients was signi cantly downregulated 12,14,15 . Moreover, researchers found that GATA1 expression level decreased in patients previously diagnosed with BCR/ABL-negative MPN during leukemia transformation 14 .…”

Section: Discussionmentioning

confidence: 79%

“…In a murine erythroleukemia cell line, Trainor et al reported that the DNA-binding domain of GATA1 can interact with the transactivation domain of p53, contributing to reciprocal inhibition between GATA1 and p53 29 . Previous studies revealed that GATA1 expression levels in megakaryocytes in primary myelo brosis was downregulated, while microarray analysis suggested that the p53 pathway was activated in megakaryocytes in primary myelo brosis, which was con rmed by quantitative reversetranscriptase PCR 12,14,15 . In our study, the GATA1 scores and GATA1 expression levels of megakaryocytes in TP53-mutated patients were signi cantly lower than those in TP53-wildtype patients.…”

Section: Discussionmentioning

confidence: 94%

“…Several studies have explored GATA1 expression level in the megakaryocytes of patients with BCR/ABL1negative myeloproliferative neoplasms (MPNs) and revealed that GATA1 expression level decreases during brotic progression and may be associated with leukemia transformation 14,15 . According to previous studies, the downregulation of GATA1 in megakaryocytes in primary myelo brosis is closely related to impaired megakaryocyte differentiation and myelo brosis 12,[16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

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GATA1 insufficiencies in dysmegakaryopoiesis of myelodysplastic syndromes

Xiao,

Li,

Zhang

et al. 2024

Preprint

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GATA1 is one of critical transcription factors for megakaryopoiesis and platelet production. Our study aimed to explore the correlations between GATA1 expression and dysmegakaryopoiesis in myelodysplastic syndromes (MDS). Data of blood cell counts, cytogenetics and TP53 mutation status from 90 MDS patients at diagnosis were collected. Firstly, we assessed GATA1 expression level of megakaryocytes by performing immunohistochemical staining on paraffin-embedded bone marrow biopsy sections from these patients. According to GATA1 expression level of megakaryocytes and positive megakaryocyte percentage, we assigned each patient a GATA1 score. Compared with TP53-wildtype patients, GATA1 scores significantly decreased in TP53-mutated patients (P < 0.001). Patients with abnormal karyotypes showed decreased GATA1 scores than those with normal karyotypes (P = 0.024). GATA1 expression levels were significantly downregulated in dysplastic megakaryocytes, especially micromegakaryocytes, compared with normal megakaryocytes (P < 0.001). Furthermore, we explored the correlation between GATA1 expression levels and cytogenetic abnormalities of the same megakaryocyte using the morphology antibody chromosome (MAC) technique on fresh bone marrow smears. We found that GATA1-negative megakaryocytes had higher frequencies of cytogenetic abnormalities. Our results indicated that decreased GATA1 expression level of megakaryocytes was significantly associated with TP53 mutations, abnormal karyotypes and dysmegakaryopoiesis in MDS, suggesting that downregulation of GATA1 expression levels of megakaryocytes plays a critical role in the pathogenesis of MDS.

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