Mutation in IDH1 gene was suggested to be associated with bad prognosis in cytogenetically normal AML (CN-AML). However, there are conflicting data about its prognostic impact. Besides, its prevalence and prognostic significance in Egyptian patients still not fully stated. We aimed to assess the prevalence of IDH1 mutation in Egyptian CN-AML patients, its correlation with FAB subtypes, and clinical outcome of those patients. Sequencing of amplified IDH1 gene exon four from 50 patients was performed to detect codon R132 point mutation. High prevalence of IDH1 mutation was detected in our patients (9/50, 18 %). Mutated IDH1 was associated with older age and higher platelets count ( = 0.04 and 0.01 respectively). The most common FAB subtype associated with mutated IDH1 was AML-M2 followed by M4. In multivariate analysis, IDH1 mutation was found as independent prognostic variable. It was significantly associated with lower CR and shorter OS ( = 0.06 and 0.009 respectively).

This study aimed to evaluate the incidence and clinical and prognostic impact of TERT A1062T mutation in AML patients treated at Mansoura Oncology Center. Screening for TERT A1062T mutation in exon 15 of the TERT gene was performed on diagnostic DNA samples from 153 AML patients and 197 healthy subjects as a control group by using sequence-specific primers. TERT A1062T mutation was detected in 18 cases out of 153 patients (11.8 %) and in one out of 197 control group subjects (0.51 %). The achievement of complete remission was significantly higher in AML group with wild type as compared to that in the mutant one (53.3 vs 16.7 %, respectively). In addition, the relapse rate was significantly higher in the mutant patients as compared to those with wild type (62.5 vs 28.2 %, respectively). The AML patients with TERT (A1062T) mutation had shorter overall survival than patients with wild type (P = 0.001). In a multivariable analysis, TERT (A1062T) mutational status is independently worse predictor factor (P = 0.007) when controlling for cytogenetic status (P = <0.001), performance status (P = <0.001) and bone marrow blast cells (P = 0.001). In conclusion, TERT A1062T mutation is an independent negative prognostic factor in AML patients. Therefore, molecular testing for TERT A1062T mutation in patients with AML is recommended in order to delineate their prognostic status.

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Background: The data about the clinical impact of NOTCH1 mutations among Egyptians B-cell chronic lymphocytic patients is not previously identified. We herein, evaluate the prevalence and the prognostic significance of neurogenic locus notch homolog protein-1 (NOTCH1) mutations in B-cell lymphocytic leukemia (B-CLL). Methods: A cohort of 105 Egyptian B-CLL patients aging from 43 to 86 years. PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline (P), glutamic acid (E), serine (S), threonine (T) (PEST domains) were sequenced by direct DNA Sanger sequencing. Results: NOTCH1 mutations were detected in 48/105 of patients (45.7%). Mutations in B-CLL patients are insertions (n=21), point mutations (n=18) and deletions (n=12). NOTCH1 mutations showed significant impact on prognosis of B-CLL patients as they were associated with increased bone marrow lymphocytes, more relapse and high incidence of mortality, shortened overall survival and progression free survival, and lymphocytes doubling time, when compared with NOTCH1 wild type B-CLL patients (P= 0.001; 0,005; 0.042; 0.049; 0.008; 0.049 respectively). Conclusion: NOTCH1 mutations were considered as bad prognostic marker in B-CLL and suggested to be included in risk stratification of B-CLL patients at diagnosis.

Background: Myelodysplastic syndromes (MDS) are complex clonal hemopoietic progenitor cell disorders that result from the evolution of aberrant clones which lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disorder. This study aimed to assess the bone marrow natural killer cells percentage as well as soluble TNF-α and sIL-32 concentration levels in MDS patients. Methods: Bone marrow samples were obtained from 34 MDS; 12 MDS-AML and 10 controls. The percentage of total NK cells and mature NK cells were determined by flowcytometry. Bone Marrow soluble TNF-α and sIL-32 concentration levels were measured by ELISA. Results: The percentage of total NK and mature NK cells were significantly lower in MDS patients as compared to controls (P<0.001). The NK cells percentages were significantly related to MDS severity scores being lowest in high score followed by intermediate score and then low score (P<0.001). Moreover; the bone marrow sTNF-α and sIL-32 levels were higher in AML-MDS group; followed by MDS group then the control group and the differences are statistically significant (P<0.001 for both). Conclusion: The reduction in NK cells might have a role in AML evolution on the top of MDS. Likewise, the bone marrow sTNF-α; and sIL32 might have a role in MDS cytopenia.