ehsan yazdandoust

Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by genetic abnormalities. These days, molecular and genetic factors are usually used as diagnostic and prognostic markers. FLT-3 is one of the most known diagnostic factors in AML. MDR1 gene belongs to the ATP binding cassette family; it is known as one of the chemotherapy-resistant causes of AML. We aimed to study FLT-3ITD mutations and their association with MDR1 gene expression in AML individuals.

For investigation, 80 AML individuals and 20 healthy controls were selected. This study was done in the cancer molecular pathology research center of Mashhad University of Medical Sciences (MUMS), Iran during 2017-2019. FLT3-ITD mutation was assessed by polymerase chain reaction (PCR); Real-time quantitative PCR was performed to measure the amount of MDR1 gene expression. Bone marrow and blood smears of patients were evaluated in terms of morphology. SPSS 16.0 was used for data analysis.

FLT3-ITD mutation and MDR1 overexpression were found in 18.8% and 23.8% of AML patients, respectively. Statistical analysis did not show any relations or association between these two markers. Cuplike morphology was observed in blast cells in 21.25% of AML cases, which was associated with FLT3-ITD mutation presence.

FLT-3 and MDR1 do not affect each other. It is suggested to perform survival studies to determine the exact role of MDR1 overexpression in drug resistance issues.

Acute lymphoblastic leukemia (ALL) accounts for nearly 30% of pediatric cancers. The maintenance treatment for ALL comprises daily oral 6-mercaptopurine (6-MP) and weekly methotrexate (MTX). 6-MP is a purine analog that can significantly improve the long-term survival of ALL patients. Despite more than 90% of 5-year survival of childhood ALL in developed countries, treatment interruption due to drug toxicities continues to be a grave concern during therapy. Several studies have highlighted the association between some genetic variants and 6-MP toxicities in ALL patients. Some variants of 6-MP metabolizing enzymes received much attention as possible predictors of myelotoxicity following 6-MP therapy. Recently, two landmark genome-wide association studies have highlighted variants in nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) as promising indicators of 6-MP toxicities. It seems that NUDT15 genotyping can help determine the optimum dose of 6-MP and prevent toxicities, especially fatal myelotoxicity. No association was found between NUDT15 variants and hepatotoxicity or survival rates of ALL patients in previous studies. However, further studies are warranted to shed more light on these issues. The current review updates and evaluates the available scientific data regarding different genetic variants of NUDT15 and their possible roles in 6-MP intolerance in various ethnic groups.

Janus kinase 2 (JAK2) and Myeloproliferative Leukemia (MPL) mutations are confirmatory indicators for Myeloproliferative Neoplasm (MPN). The current study was performed to determine the frequency of MPL mutation in MPN patients without JAK2 mutation, in order to assign MPL mutation frequency in North-East of Iran. Total of 105 negative JAK2 cases including 5 Myeloproliferative Disorders (MPD), 15 Polycytemia Vera (PV) and 15 Essential Thrombocytosis (ET) who referred to Qaem Medical Center were assigned to this study. ARMS-PCR was carried out for measuring MPL mutations. A significant difference was observed between MPL mutant and non-mutant groups from overview of MPL mutation (P=0.00001). From the total studied population, 14.28% were ET cases and 4.71% of them had splenomegaly. About 66.66% had thrombocytosis and 33.33% of all the individuals had leukocytosis according to WHO criteria, and 4.76% of non-MPL mutant individuals had splenomegaly (P=1).
This mutation was reported in 4-6% of ET and PMF individuals. In this research, 4.76 % of studied individuals had MPL (W515L/K) mutation, which were diagnosed with ET. Generally, the presence of JAK2 and MPL mutations are the most important criteria for MPN diagnosis. The obtained frequency of MPL mutation was similar to previous studies. Despite the high frequency of JAK2 and Philadelphia abnormality, MPL mutation was rare in myeloprolifrative disorders. Further studies are suggested to investigate its prognostic effects for these diseases.

Brain and Acute Leukemia Cytoplasmic (BAALC) is a gene which its expression is confined to progenitor cells; therefore, no expression has been illustrated in mature cells of bone marrow or white blood cells (WBC). In addition, high BAALC expression is associated with poor prognosis in Acute Myeloid Leukemia (AML) individuals and is considered as an important risk factor in Cytogenetic Normal Acute Myeloid Leukemia.
This retrospective study was designed to evaluate prognostic importance of BAALC gene expression in pediatric AML patients. Recently, recognized 114 AML Iranian children with age range of 1-15 years were entered in this study during 2012-2015. Real-Time PCR was applied for BAALC gene.
High BAALC gene expression was detected in 47 patients (41.2%) and low expression in 67 patients (58.8%). High BAALC gene expression group (n=47) contained23 males and 24 females. All patients were followed up for 2 years to measure disease prognosis. BAALC expression was a main unfavorable prognostic factor in AML patient’s especially normal karyotype. AML cases with high BAALC expression had considerable further cumulative risk after 25 months; it was 39 months in low expressed cases. All of cytogenetic normal acute myeloid leukemias (CN-AML) and high BAALC expressed patients died. High BAALC expression in AML cases was associated with considerable shorter overall survival (OS).
According to our findings, BAALC expression is a significance poor prognostic factor in AML patients with normal karyotype. This study suggests new therapeutic strategies to ameliorate the treat rate of AML patients. Further research with longer follow up and larger sample size is required to definite statistical perusals.

Acute myeloid leukemia (AML) is a malignant disorder involving blood cells, characterized by obstructed or distorted differentiation of hematopoietic stem cells. In cytogenetically normal AML (CN AML), molecular abnormalities in NPM, FLT3, CEBPA, and BAALC genes are observed. Initially, high BAALC (Brain and Acute Leukemia Cytoplasmic gene) expression was introduced in a study on AML cases with trisomy 8. The present systematic review aimed to determine the prognostic value of BAALC expression in CN-AML patients within the age range of 1 month to 15 years.
In this systematic review, scientific databases including PubMed, Scopus, Embase, ISI, and Cochrane Library were searched. All the evaluated retrospective studies focused on the prognostic value of BAALC expression.
Overall, BAALC expression was reported in 30-60% of AML patients (mean=45%). High expression of BAALC gene was reported in M0, M1, and M2 subtypes of pediatric AML. In only one study, in addition to these subtypes, M4 was also reported (12.5% of cases).
This systematic review resulted in a significant association between high BAALC expression and poor response to chemotherapy in pediatric AML. However, OS (Overall Survival) and EFS (Event - Free Survival) findings were contradictory, relapse and death increase in the presence of high BAALC expression. Therefore, BAALC expression could be considered as a clinical prognostic marker for the treatment of AML patients. Further efficient prognostic indicators should be identified in order to gather information about therapeutic strategies for AML and risk analysis in these patients.