Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics.

Aim: This study explores the prognostic impact of FLT3-ITD, NPM1, and WT1 mutations both independently and in combination in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) patients as they exhibit varying clinical outcomes.

Methods: 150 CN-AML patients were selected to assess the prevalence and prognostic significance of WT1 mutations in combination with FLT3-ITD and NPM1 status using polymerase chain reaction (PCR) followed by Sanger sequencing.

Results: WT1 exon 7 mutations were present in 12.

Double Philadelphia chromosome: a rare and sole abnormality in pediatric B-acute lymphoblastic leukemia.

The present study describes a 7-year-old male child who had attended the Pediatric Oncology Clinic of the Regional Cancer Centre, Thiruvananthapuram, Kerala, India, and was pathologically confirmed to have B-Acute Lymphoblastic Leukemia (B-ALL). Conventional cytogenetics analysis at diagnosis showed the presence of a double Philadelphia chromosome and the karyotype of the case was 47, , (9;22)(q34;q11.2), + der(22)t(9;22).

MicroRNA-based therapies: Revolutionizing the treatment of acute myeloid leukemia.

MicroRNAs (miRNAs) are small noncoding epigenetic regulators that exert critical significance by influencing target mRNAs and governing gene expression patterns and cellular signaling pathways. miRNAs play a pivotal role in a wide array of biological processes, including cell differentiation, proliferation, and survival. Numerous miRNAs contribute to tumorigenesis and cancer progression by promoting tumor growth, angiogenesis, invasion, and immune evasion, while others exert tumor suppressive effects.

Acute myeloid leukemia patients with variant or unusual translocations involving chromosomes 8 and 21 - A comprehensive cytogenetic profiling of three cases with review of literature.

Background: t(8;21)(q22;q22) is the most frequent recurrent translocation in acute myeloid leukemia (AML) resulting in an in-frame fusion of RUNX1/RUNX1T1 that regulates various genes involved in the signaling pathways. This leukemogenic alteration is usually associated with a favorable clinical outcome. Variants of t(8;21) can be formed involving a third or fourth chromosome in ~3-4% of t(8;21)-AML.

Hyperdiploid Multiple Myeloma with Novel Complex Structural Chromosome Abnormalities Associated with Poor Prognosis : A Rare Case Report.

Hyperdiploid multiple myeloma (MM) is associated with better prognosis and non-hyperdiploid subtype is associated with variable to adverse prognosis based on the nature of karyotype abnormality.  Rarely exceptions to this hyperdiploid and non-hyperdiploid divisions do exist in a minority. We report an adult male MM patient who showed hyperdiploid karyotype with few novel complex abnormalities and who showed poor clinical outcome.

A concise review on the molecular genetics of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults that affects the myeloid lineage. The recent advances have upgraded our understanding of the cytogenetic abnormalities and molecular mutations associated with AML that further aids in prognostication and risk stratification of the disease. Based on the highly heterogeneous nature of the disease and cytogenetic profile, AML patients can be stratified into favourable, intermediate and adverse-risk groups.

Whole Exome Sequencing Identifies Cohesin Component STAG1 Mutation in de novo Acute Myeloid Leukemia (FAB M2): A Pilot Study with Cytogenetics, Clinical and Prognostic Implications.

The clinical implications of cohesin gene complex mutation in acute myeloid leukemia (AML) are not well characterized. In the present study, a cohort of 152 de novo unselected adult AML patients underwent conventional and molecular cytogenetic analysis for chromosomal aberrations. Further, we examined the frequency and clinical implications of mutations in cohesin gene complex STAG1, STAG2, RAD21, SMC1, and SMC3 using whole exome sequencing as a pilot study in 10 de novo patients with AML-FAB M2.

L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide Oxidative Stress in Human Acute Promyelocytic Leukemia Cells.

Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (AsO) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in AsO chemotherapy using human leukemia (HL-60) cells. assays on the cytotoxicity of AsO and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed.

Prognostic Implications of DNA Repair, Ploidy and Telomerase in the Malignant Transformation Risk Assessment of Leukoplakia.

Background: Although leukoplakia shows a higher risk for malignant transformation to oral cancer, currently there are no clinically relevant biomarker which can predict the potentially high risk leukoplakia. This study aimed to investigate the genetic alterations such as DNA ploidy, telomerase expression and DNA repair capacity as predictive markers of malignant transformation risk of leukoplakia.

Methods: The study was initiated in September 2005 and patients were followed up to March 2014.

Differential gene expression changes and their implication on the disease progression in patients with Chronic Myeloid Leukemia.

The molecular mechanisms responsible for disease progression of CML are not conclusive. The main functional changes associated with disease evolution in CML was high proliferation rate, decreased apoptosis, blockade of differentiation, and strong resistance to chemotherapeutic agents. The current study analyzed the relative expressional profiles of genes related with proliferation, apoptosis, differentiation, and resistance to chemotherapeutic agents such as c-MYC, BAD, BCL-2, C/EBPα/-β and ABCB1 respectively in different clinical stages of CML by SYBR Green I quantitative real-time (qRT) PCR.

Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia.

The emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/ positive chronic myeloid leukemia (CML), is considered to be a feature of disease evolution. However, their frequency of incidence, impact on prognosis and treatment response effect in CML is not conclusive. In the present study, we performed a chromosome analysis of 489 patients in different clinical stages of CML, using conventional GTG-banding, Fluorescent Hybridization and Spectral Karyotyping.

Genomic amplification of BCR-ABL1 fusion gene and its impact on the disease progression mechanism in patients with chronic myelogenous leukemia.

Identification of BCR-ABL1 fusion gene amplification status is critically important in the effective management of chronic myelogenous leukemia (CML) patients. Earlier reports suggested that overexpression of BCR-ABL1 either through amplification of BCR-ABL1 fusion gene or by the up regulation of BCR-ABL1 transcript level might be an early phenomenon in the establishment of IM resistance and disease evolution in CML. In the current study, we performed dual color dual fusion locus specific BCR/ABL1 FISH analysis along with karyotype analysis using GTG banding (G-banding using trypsin and Giemsa) technique in 489 patients with different clinical stages of CML at diagnosis or during the course of the disease to unravel the spectrum of BCR-ABL1 fusion gene amplification status.

Prognostic Implications of Derivative Chromosome 9 Deletions in Patients with Advanced-Stage Chronic Myelogenous Leukemia.

Elucidation of cryptic BCR/ABL1 gene rearrangement is exceptionally important in the clinical diagnosis and prognosis of chronic myelogenous leukemia (CML). Previous reports indicated an adverse prognostic effect of atypical BCR/ABL1 gene rearrangements with submicroscopic ABL1-BCR deletions on derivative chromosome 9 [der(9)] in CML patients. Dual color dual fusion locus-specific BCR/ABL1 fluorescent in situ hybridization (FISH) analysis together with G-banding using trypsin and Giemsa (GTG banding) was performed in 489 patients at different stages of CML to investigate the spectrum of BCR/ABL1 gene rearrangements.

Regulatory players of DNA damage repair mechanisms: Role in Cancer Chemoresistance.

DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage.

Isodicentric Philadelphia Chromosome: A Rare Chromosomal Aberration in Imatinib-Resistant Chronic Myelogenous Leukemia Patients - Case Report with Review of the Literature.

The BCR-ABL1 fusion gene derived from the Philadelphia chromosome, resulting from a classical translocation event t(9;22)(q34.13;q11.23), is responsible for the pathogenesis of chronic myeloid leukemia (CML) in more than 90% of the patients.

Enigmatic Inv(9): A Case Report on Rare Findings in Hematological Malignancies.

Introduction: Inversion of chromosome 9 had been widely discussed among geneticists and evolutionary biologists because of its significant impact on various hereditary disorders and in the evolution of man. The role of such inversions in human disease evolution is an area hitherto unclear.

Case Presentation: We present the case of a chronic myeloid leukemia (CML) patient who showed intermittent relapse on treatment, with a rare appearance of clones with dual inversion (9) breakpoints [inv(9)(p22q34); inv(9)(p11q21)].

A Case Report of Concurrent IDH1 and NPM1 Mutations in a Novel t(X;2)(q28;p22) Translocation in Acute Myeloid Leukaemia without Maturation (AML-M1).

Acute myeloid leukaemia (AML) is one of the fatal haematological malignancies as a consequence of its genetic heterogeneity. At present, the prediction of the clinical response to treatment for AML is based not only on detection of cytogenetic aberrations but also by analysing certain molecular genetic alterations. There are limited in sights into the contribution, disease progression, treatment outcome, and characterisation with respect to the uncommon chromosomal abnormalities leading to AML.

Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation.

Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients.

The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial role in the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the target of genetic alterations and were associated with clinical complexity among AML. We here analyze the frequency and types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried to find out associations of these variations with different clinical parameters and the prognostic significance in AML.

A novel chromosomal abnormality t (9;14)(p24;q13) in B-acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. We describe the clinical, morphologic, immunophenotypic and cytogenetic findings in the case of a 26-year-old man with B-lymphoblastic leukemia. Surface marker analysis revealed that they are positive for CD markers CD10, CD19, CD13, CD34, CD45 and HLA-DR, but negative for CD20, CD33, CD117 and CD11C markers.

Novel t(7;10)(p22;p24) along with NPM1 mutation in patient with relapsed acute myeloid leukemia.

Chromosomal abnormalities/genetic mutations associated with hematological malignancies alter the structure and function of genes controlling cell proliferation and differentiation through multiple and complex pathways, resulting different clinical outcomes. This is a case study of a lady presented with acute myeloid leukemia (AML M1) at our center who relapsed 10 years after the induction therapy. Cytogenetic and molecular analyses were performed in this case at the time of relapse to find out the chromosomal abnormalities and genetic abnormalities like FMS-like tyrosine kinase (FLT3) and nucleophosmin (NPM1) mutation.

Recurrent isochromosome 21 and multiple abnormalities in a patient suspected of having acute myeloid leukemia with eosinophilic differentiation -- a rare case from South India.

Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia(Ph) chromosome as the major abnormality.

Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) polymorphisms in familial and sporadic breast cancer predisposition and survival: an Indian report.

The etiology of a significant proportion of familial breast cancers is still poorly understood, with known high penetrance gene mutations accounting for only a small proportion of the cases. The increased risk of breast cancer for the majority of women with a family history likely reflects shared minor low penetrant genetic factors. In the present case-control study undertaken to examine the influence of DNA damage repair gene polymorphisms in familial and sporadic breast cancer susceptibility, 219 Sporadic and 140 familial breast cancer patients and 367 controls were genotyped using PCRRFLP.

Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients.

The glutathione S-transferases (GSTs) are a superfamily of genes whose products are phase II enzymes, catalyzing the conjugation of reactive intermediates to soluble glutathione. Some of the GSTs are polymorphic and may play a role in lung cancer susceptibility. We investigated whether genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes modulated lung cancer risk and affect survival among lung cancer patients.

Prognostic importance of DNA repair gene polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln in lung cancer patients from India.

Purpose: Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive.

Methods: In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population.