Among Acute Myeloid Leukemia Research Articles

MDM2 T309G has a Synergistic Effect with P21 ser31arg Single Nucleotide Polymorphisms on the Risk of Acute Myeloid Leukemia

The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically

Valproic acid (VPA) has extensive effects on leukemic blasts through its inhibition of histone deacetylases. The main goal of this study was to identify the subgroup of patients who may benefit most from VPA treatment. We examined the significance of t(8;21) chromosomal aberration for VPA treatment response among acute myeloid leukemia (AML) patients by direct comparison of AML1/ETO-negative vs. positive leukemic cell-lines as well as bone marrow blasts from AML patients. In t(8;21) AML, leukemogenesis is supposed to be induced via aberrant recruitment of histone deacetylases. AML cell lines of different genotypes (Kasumi-1, Kasumi-6, MV4;11, K562) and diagnostic bone marrow samples from patients were treated with VPA. VPA induced apoptosis in AML1/ETO-positive and MLL–AF4-positive cells in a dose-dependent manner. Differentiation, as indicated by changes in immunophenotype, was observed only in AML1/ETO-positive cells. VPA increased the expression of AML1 target genes – PU.1, C/EBPa, BPI and IGFBP7 only in AML1/ETO-positive cells. This AML1/ETO-specific effect was confirmed also using patient blasts isolated at the time of diagnosis. AML1/ETO-positive leukemia shows specific mechanism of VPA residing from differentiation followed by apoptosis that is accompanied by an increase in the expression of repressed AML1 target genes. Our data suggest that AML1/ETO-positive patients might derive the greatest benefit from VPA treatment.

Improved Survival Rates Among Acute Myeloid Leukemia (AML) Patients 65 to 74 Years: Population-Based Estimates Over Three Decades,

Abstract 3591 Background:AML is the common acute leukemia in adults, accounting for approximately 90% of all acute leukemias in those over the age of 18 years. Overall survival remains poor, with <50% 5-year survival in patients under 45 years and <5% in those over 65 years. We examined whether there has been improvement in survival over three successive decades for subsets of geriatric AML patients. Methods: Examining data from the Surveillance, Epidemiology and End Results (SEER) database, we determined relative overall survival (+/− standard error) of patients with AML 65–74, 75–84 and 85+ years of age between 1977–86, 1987–96 and 1997–2006. Results: Survival for both males and females at 12, 24 and 36 months post-diagnosis is shown below. Between 1977–1986 and 1987–1996, 12-month, 24-month and 36-month survival rates increased from 20% to 25%, 10% to 13.1%, and 5.5 to 8.4%, respectively, in the 65–74 year age group. Between 1987–1996 and 1997–2006, 12-month, 24-month and 36-month survival rates increased from 25% to 30%, 13% to 17% and 8.4% to 11.7%, respectively, in the same age group. Survival rates increased over each decade in patients younger than 75 years of age, but did not improve significantly in patients 75 years and older. Female patients exhibited better survival up to 24 months than males in all age categories. The oldest-old (85+ years) had the lowest survival rates, with no apparent improvement over the past 3 decades for either gender. Conclusions: Analysis of a large data-set demonstrated that overall survival remains unsatisfactory over a 3-decade period among older patients, but has in fact improved in the young-old (65–74 year age group). Neither standard nor newly developed chemotherapy regimens have favorably impacted survival for the oldest-old AML patients, and intervention in this age group is best undertaken on a clinical trial.Table:Relative Survival Rates for Acute Myeloid LeukemiaSurvival ± Standard Error % (Male)Survival ± Standard Error % (Female)Age (yrs)12 months24 months36 months12 months24 months36 monthsYear (1977 to 1986)Year (1977 to 1986)All29.1±0.90 (n=2973)16.1±0.711.4±0.631.3±1.0 (n=2420)18.7±0.814.3±0.865 to 7420.1±1.5 (n=727)10.0±1.25.5±0.916.3±1.7 (n=490)9.6±1.45.5±1.175 to 8410.3±1.3 (n=584)3.3±0.82.3±0.714.9±1.6 (n=531)7.8±1.25.0±1≥8510.6±2.7 (n=160)7.0±2.44.4±2.29.3±2.1 (n=224)5.3±1.73.4±1.5Year (1987 to 1996)Year (1987 to 1996)All34.8±0.8 (n=3360)20.7±0.716.5±0.736.0±0.9 (n=2861)24.1±0.819.9±0.865 to 7425.1±1.5 (n=913)12.3±1.17.5±0.926.1±1.8 (n=607)14.0±1.49.4±1.275 to 8411±0±1.3 (n=660)4.1±0.82.7±0.711.6±1.3 (n=608)6.2±1.03.9±0.9≥856.8±2.2 (n=159)1.7±1.20.0±04.8±1.4 (n=264)1.9±0.91.1±0.8Year (1997 to 2006)Year (1997 to 2006)All39.1±0.8 (n=4078)27.4±0.823.7±0.840.9±0.9 (n=3480)30.5±0.926.9±0.965 to 7430.3±1.6 (n=943)15.8±1.39.8±1.130.7±1.9(n=662)18.4±1.613.7±1.575 to 8414.8±1.3 (n=896)5.0±0.83.5±0.814.9±1.3(n=831)6.4±0.93.3±0.70≥857.8±1.8 (n=268)1.7±11.2±0.87.3±1.5(n=364)1.0±0.70.6±0.6 Disclosures:No relevant conflicts of interest to declare.

RAD51 and XRCC3 Gene Polymorphisms and the Risk of Developing Acute Myeloid Leukemia

RAD51 (Rec A homolog of E.coli) is a polymorphic gene and one of the central proteins in homologous recombination-DNA-double-stand breaks (HR-DNA-DSB) repair pathway, which is vital in maintaining genetic stability...

Levels of interleukins 12 (IL-12) and 13 (IL-13), hepatitis B and C serology, and blood cultures among acute myeloid leukemia (AML) patients in Egypt

There is an interest in the use of IL-12 as a possible anti-cancer drug to induce immune responses and anti-IL-13 formulations to treat the undesirable effects of IL-13. Thus, the present study aimed at analyzing IL-12 and IL-13 profiles, viral hepatitis serology and blood cultures in acute myeloid leukemia (AML) patients. Forty individuals (20 without septicemia - Group A, and 20 with septicemia - Group B) and 20 healthy controls were evaluated. Hepatitis B virus antigens (HBsAg) and hepatitis C virus antibodies (HCV Ab) were quantified using commercial ELISA kits. IL-12 and IL-13 levels were estimated in culture supernatant of mitogen-stimulated peripheral blood mononuclear cells by ELISA. Significantly low IL-12 values were observed among AML patients compared to controls whereas the opposite was observed regarding IL-13. IL-12 levels were found to be elevated in the follow-up cases. M4 and M5 subtypes of AML presented higher IL-12 levels than M1 and M2 subtypes. The isolated organisms from AML with septicemia were Staphylococcus aureus (35%), Esherichia coli (25%), coagulase-negative staphylococci (25%), and Candida (15%). Fungemia cases showed higher IL-12 values than bacteremia cases. In conclusion, IL-12 and IL-13 should be further tested in large-scale studies to provide future immunotherapy against AML.