Prevalence and impact of colony stimulating factor 3 receptor (CSF3R) mutations among Egyptian acute myeloid leukemia patients

Aref, Salah; El‐Ghonemy, Mohamed Sabry; Abouzeid, Tarek; El-Sabbagh, Amr Mohamed; Elbaiomy, Mohamed

doi:10.1016/j.leukres.2014.03.020

Cited by 5 publications

(5 citation statements)

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“…In the largest published series to date, candidate gene sequencing of 15 genes in 30 cases of SCN-AML/MDS showed that 27 (90%) had truncation mutations of CSF3R , encoding the G-CSF receptor (G-CSFR), and 19 (63%) had mutations in RUNX1 (17). These data are consistent with prior studies showing that truncations mutations of CSF3R are present in approximately 80% of cases of SCN-AML/MDS (18, 19). In contrast, monosomy 7, RUNX1 , and CSF3R mutations are relatively uncommon in de novo AML (18).…”

Section: Leukemic Transformation In Scnsupporting

confidence: 93%

Mechanisms of leukemic transformation in congenital neutropenia

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2019

Current Opinion in Hematology

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Purpose of review The development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia is now the major cause of mortality. Treatment options are limited and there are no effective prevention strategies. This review focuses on mechanisms of leukemic transformation in severe congenital neutropenia (SCN) and Shwachman Diamond syndrome (SDS), the two most common types of congenital neutropenia. Recent findings AML/MDS that develops in the setting of congenital neutropenia has distinct molecular features. Clonal hematopoiesis due to TP53 mutations is seen in nearly 50% of patients with SDS, but is not seen in patients with SCN. Accordingly, there is a very high frequency of TP53 mutations in AML/MDS arising in the setting of SDS but not SCN. The rate of mutation accumulation in hematopoietic stem cells (HSCs) from patients with congenital neutropenia is not increased. Summary Both HSC cell-intrinsic and non-cell intrinsic changes contribute to the development of clonal hematopoiesis in congenital neutropenia and likely accounts for the high rate of leukemic transformation. In SCN, the persistently high levels of G-CSF drive expansion of HSCs carrying truncation mutations of CSF3R. In SDS, impaired ribosome biogenesis induces p53-mediated growth inhibition and drives expansion of HSCs carrying TP53 mutations.

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Section: Leukemic Transformation In Scnsupporting

confidence: 93%

Mechanisms of leukemic transformation in congenital neutropenia

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2019

Current Opinion in Hematology

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“…Several studies had shown that AML patients with CEBPA mutations had a higher mutation rate of CSF3R. 13,18 The majority of AML patients with CSF3R mutations had abnormalities in either CBF genes or CEBPAdm. 12,15,18 The high mutation rate (41.7%) of CEBPA in patients with mutant CSF3R was also found in our study.…”

Section: Discussionmentioning

confidence: 99%

“…13,18 The majority of AML patients with CSF3R mutations had abnormalities in either CBF genes or CEBPAdm. 12,15,18 The high mutation rate (41.7%) of CEBPA in patients with mutant CSF3R was also found in our study. Moreover, the RUNX1-RUNX1T1 translocation has a high degree of overlap with CSF3R modifications.…”

Section: Discussionmentioning

confidence: 99%

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The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations

Chen

Fang

et al. 2021

Int J Lab Hematology

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Introduction:The colony-stimulating factor 3 receptor (CSF3R) controls the proliferation of myeloid progenitors and differentiation into neutrophils. However, the clinical features and prognostic significance of CSF3R mutations in primary acute myeloid leukemia (AML) patients are still unclear.Methods: 158 newly diagnosed AML patients were retrospectively evaluated in our study. Amplicon-based next-generation sequencing (NGS) and multiplex-nested reverse-transcription polymerase chain reaction (RT-PCR) were used to investigate the 34 genes and 43 fusion genes associated with leukemia. In addition, clinical features, mutation incidence, and survival outcomes were compared between patients with CSF3R mutation and patients with wild-type CSF3R.Results: In our study, CSF3R mutations were found in 7.6% (12/158) cases. The membrane-proximal amino acid substitution T618I (58.3%) was the most frequent mutation. CSF3R mutations were associated with higher WBC counts (P = .035).CEBPA mutation, TET2 mutation, and RUNX1-RUNX1T1 translocation were the most common co-mutations of CSF3R. The CSF3R gene was mutually exclusive with signal transduction genes (P = .029), while positively associated with TET2 mutations (P = .014). CSF3R mutations had no effect on CR1 (P = .935), R (P = .625) and OS (P = .1172). Patients with CSF3R mutations had a worse DFS (P = .0352) than those with wild-type CSF3R. Multivariate survival analysis showed that CSF3R mutation was an independent risk factor for DFS of primary AML patients (HR=2.048, 95%CI:1.006-4.170, P = .048). Conclusion:AML patients with CSF3R mutations had unique clinical features and gene co-mutation spectrum. CSF3R mutation was an independent risk factor for DFS and could be a potential prognostic marker and therapeutic target for Chinese primary AML patients.

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“…Although many recurrent genetic lesions have been identified, no single mutation is enough to stimulate leukemogenesis. Novel molecular genetic methodologies and genomic sequencing of leukemic cells will help improve the understanding of the pathogenesis of AML and identify novel therapeutic targets (Aref et al, 2014;Aref et al, 2015;Pourrajab et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Implications of Glutathione Peroxidase 3 Expression in a Cohort of Egyptian Patients with Acute Myeloid Leukemia

Shaaban

Aref

Taalab

et al. 2020

Asian Pac J Cancer Prev

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Background: The impact of low expression of Glutathione peroxidase 3 (GPX3) on the clinical course of acute myeloid leukemia (AML) is poorly investigated. Aims: To explore the status of GPX3 expression and analyze its clinical characteristics and prognosis in a cohort of Egyptian patients with AML. Methods: GPX3 mRNA level was assessed by RT-q PCR in 40 newly diagnosed AML patients and 10 healthy controls. Results: The gene expression level was significantly lower in AML patients than the control group (P < 0.001). A cut off value (0.1223) for the discrimination between AML and controls was obtained by ROC curve. According to this cutoff value; the patients were reassigned into 2 groups; 28 patients with lower GPX3 expression and 12 patients with high GPX3 expression. GPX3 low expression was significantly associated with higher incidence of induction death (P= 0.037) and lower CR rate (P=0.048). Moreover, GPX3 low expression was significantly associated with shorter cumulative 1-year overall survival (OS) (P = 0.001) and disease-free survival (DFS) (P=0.028). Conclusion: GPX3 low expression status is considered a poor prognostic factor in AML predicting shorter OS and DFS. The study highlights the importance of targeting glutathione metabolism as a central component of the anti-leukemia therapy.

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Prevalence and impact of colony stimulating factor 3 receptor (CSF3R) mutations among Egyptian acute myeloid leukemia patients

Cited by 5 publications

References 22 publications

Mechanisms of leukemic transformation in congenital neutropenia

Mechanisms of leukemic transformation in congenital neutropenia

The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations

Implications of Glutathione Peroxidase 3 Expression in a Cohort of Egyptian Patients with Acute Myeloid Leukemia

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