ABSTRACT
HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.
ABSTRACT
OBJECTIVE: IDH mutations diversely affect the prognosis of cyogenetically normal acute myeloid leukemia (CN-AML) adult patients. The aim of this study is to assess the frequency of IDH mutations and to evaluate its role in AML prognosis. METHODS: We have analyzed IDH1 and 2 mutations using High Resolution Melting curve analysis (HRM) in 70 denovo AML patients. RESULTS: The median age of AML patients is 40 years (16-75). Incidence of IDH mutations is 10/70 (14.3%); 2 (2.9%) IDH1 mutant and 8 (11.4%) IDH2 mutant. Median PB blasts of mutant IDH patients was 67.5% (25-96) vs. 44% (0-98) for wild type (p=0.065). Eight/10 (80%) mutant IDH patients had B.M blasts ≥50% vs. 2/10 (20%) <50% (p<0.001) and were classified as intermediate risk cytogenetics (p=0.020) with wild FLT3-ITD (p=0.001). Ten/10 (100%) mutant IDH patients showed wild NPM1 (p=0.049). Median OS of mutant IDH in the intermediate risk cytogenetics was 1.8 years (0.7-3.1) vs. 3.1 years (1.1-5.5) for wild IDH (p=0.05). CONCLUSION: IDH mutation is mainly associated with intermediate risk AML and when integrated in this specific subgroup displays a lower survival and can be considered an additional integrated molecular risk marker for AML prognosis.
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Subject(s)
Isocitrate Dehydrogenase/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Adolescent , Adult , Aged , Female , Humans , Karyotyping , Male , Middle Aged , Nucleophosmin , Risk Factors , Young AdultABSTRACT
JAK2, CALR, MPL and triple-negative mutational status has a direct impact on symptom severity and disease burden assessed by MPN10 score in myeloproliferative neoplasms (MPNs). Among 93 patients; median MPN10 score was 48 (5-76) in JAK2 mutants versus 25 (4-80) in JAK2 negative (p < .001); 22.5 (4-65) in CALR mutants versus 35 (5-80) in CALR negative (p < .050) and 21 (10-48) in triple negative versus 40 (4-80) in JAK2/CALR/MPL mutants (p < .001). At three years, progression free and overall survival of JAK2-positive versus JAK2-negative patients were 62% versus 100% (p < .001); 85% versus 100% (p = .011) and were 100% versus 78% (p = .067); 100% versus 92% (p = .197) in CALR-positive versus CALR-negative patients and 100% versus 75% (p = .004); 100% versus 90% (p = .015) in triple negative versus mutant patients, respectively. MPN10 score in association with driver gene mutations can be used as a predictor of survival in MPN patients.
