Chandrakala Shanmukhaiah's research while affiliated with King Edward Memorial Hospital and other places

Publications (23)

Article
Full-text available
Purpose Immune thrombocytopenia (ITP) is primarily considered a bleeding disorder; its impact on patients’ health-related quality of life (HRQoL) is under-recognized. We aimed to assess how aligned patient and physician perceptions are regarding ITP-associated symptoms, HRQoL, and disease management in India. Methods Patients and physicians (hemat...
Article
Full-text available
Background Myelodysplastic syndromes (MDS) is defined as heterogenous disease, it contains heterogenous leukemic stem cells with various degree of cell differentiation. The perturbation of genes involved in myeloid progenitor cell growth, differentiation and proliferation lead to morphologic dysplasia, maturation arrest, ineffective hematopoiesis h...
Article
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Background: The bispecific monoclonal antibody emicizumab bridges activated factor IX and factor X, mimicking the cofactor function of activated factor VIII (FVIII), restoring hemostasis. Objectives: The Phase 3b STASEY study was designed to assess the safety of emicizumab prophylaxis in people with hemophilia A (HA) with FVIII inhibitors. Meth...
Article
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Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients. We have studied 152 MDS patients using cytogene...
Preprint
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The tyrosine kinase inhibitor (TKI) therapy has a high response rate in chronic myeloid leukemia (CML). However majority of patients relapse due to high mutation susceptibility of tyrosine kinase domain (TKD) of BCR/ABL fusion gene. We report a case of CML which was diagnosed and monitored for 10 years as per the ELN guidelines. Mutational analysis...
Article
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Introduction: Type 3 Von Willebrand Disease (VWD) is the least common but the most severe form of a disease, with a prevalence of about 0. 5 to 1 per million in Western countries. The prevalence of type 3 VWD in the developing countries, with a high degree of consanguinity, is about 6 per million. Moreover, due to underdiagnosis of the milder cases...
Article
Introduction von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement thera...
Preprint
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Autoimmune lymphoproliferative syndrome (ALPS) is caused due to defects in the Fas-mediated apoptotic pathway. This disease is characterised by chronic non -malignant lymphoproliferation, autoimmune cytopenias and accumulation of double-negative T cells. FAS is the most commonly affected gene observed in patients with ALPS. There is a paucity of da...
Article
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Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We pres...
Preprint
Full-text available
Background: Immune thrombocytopenia (ITP) is primarily considered a bleeding disorder; its impact on patients’ health-related quality of life (HRQoL) is under-recognized. We aimed to assess how aligned patient and physician perceptions are regarding ITP-associated symptoms, HRQoL, and disease management in India. Methods: Patients and physicians (h...
Article
Full-text available
The resistance for the tyrosine kinase inhibitors in chronic myeloid leukemia (CML) occurs mainly due to BCR/ABL1 dependent and independent mechanisms. The defective DNA repair due to functional polymorphisms in DNA repair genes, might act as an etiological factor for leukemia progression. The study was carried out to understand the role of DNA rep...
Article
Inter-individual variability to Imatinib response among chronic myeloid patients has led to the hunt for mechanisms responsible for such variability. Screening of single nucleotide polymorphisms (SNPs) in transmembrane transporter genes is a common approach employed to decipher its role in influencing the pharmacokinetics of Imatinib. The focus of...
Article
Myelodysplastic syndromes (MDSs) are heterogeneous clonal haematopoeitic stem cell disorders characterized by ineffective haematopoeisis, cytopenias and risk of progression to AML. We studied 150 MDS patients for cytogenetic aberrations and 60 patients with normal karyotype and 40 patients harboring cytogenetic abnormalities for copy number variati...
Article
Full-text available
Myelodysplastic syndromes (MDSs) are heterogeneous hematopoietic disease characterized by ineffective haematopoiesis that frequently transforms into acute leukaemia. Alterations in many individual biologic pathways have been reported in MDS pathophysiology. Disease progression along the MDS, acute myeloid leukemia (AML) continuum is believed to be...
Article
Co-inheritance of triplicated α-genes can alter the clinical and hematological phenotypes of β-thalassemias. We evaluated the phenotypic diversity and transfusion requirements in β-thalassemia heterozygotes, homozygotes, and normal individuals with associated α-gene triplication. Clinical and hematological evaluation was done and the β-thalassemia...
Article
Full-text available
Acute Myeloid Leukemia is often called as stem cell disease that presents with treatment failure and poor disease outcome. Leukemic stem cells in AML are enriched in Lineage-/CD38-/CD34+ compartment of CD34 positive AML. Many markers important for stem cell biology have been reported for their association with leukemic stem cell population but what...
Article
Full-text available
Mutations in the ABL kinase domain and SH3-SH2 domain of the BCR/ABL gene and amplification of the Philadelphia chromosome are the two important BCR/ABL dependent mechanisms of imatinib resistance. Here, we intended to study the role played by TKI, imatinib, in selection of gene mutations and development of chromosomal abnormalities in Indian CML p...

Citations

... However, the proposed prognostic systems has limitation in predicting clinical course of some patients followed by their management too, prompting for continuous need of improvement in these systems. Recently large number of studies [5][6][7][8] performed, to investigate gene mutation effect on clinical course of MDS and incorporated in available prognostic model. ...
... severity, suffering, and prognosis) are interpreted according to the observer's socio-economic status, race, previous experience, and level of education. Patients, caregivers, and health care providers may have differing perceptions of a specific disease even though they all observe the same progression [56,57]. Specifically, family and friends tend to overestimate the suffering experienced by ET patients as compared to the patient's own ratings [57]. ...
... FA-I cases comprise approximately 1% of all FA cases and have been associated with at least three features of VACTERL-H [123], a rare disease that affects multiple body systems. Recently, an eight-year-old male with aplasia referred for a diagnosis of FA was reported to harbour germline homozygous FANCI c.1813C>T [124]. FANCD2 ubiquitination was not detected in peripheral blood cells from this patient and increased chromosomal breakage was observed, suggesting abrogation of the FA pathway. ...
... It plays a role in the regulation of intravascular fibrinolysis [1]. Decreased levels of A2-AP will lead to increased capacity of the fibrinolytic function and subsequent bleeding symptoms due to insufficient or no inhibition of plasmin [2]. Congenital alpha-2 antiplasmin deficiency is an extremely rare autosomal recessive disease; the real prevalence is not known [3,4]. ...
... Annamaneni et al. 11 studied the XRCC1 effect on CML and polymorphisms of XRCC1, codon 399, 280 and 194; similarly, no significant difference was detected. Dhangar et al. 12 investigated the correlation between clinical response to therapy between CML and XRCC1 rs1799782, rs25487, and ERCC2 rs13181 polymorphisms; no significant relationship was found. Banescu et al. 13 also examined the relationship between CML and XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC3 r241Met, and ERCC2 Lys751Gln polymorphisms and showed that the ERCC2 Lys751Gln genotype increases the risk of CML. ...
... We also found 13 variants of DKC1 in Asia with 100% male (7,9,13,20,23,28,32,35,36,40), 52 variants in non-Asia with 84.8% male (1, 8, 10-14, 16-19, 21, 24-26, 29, 31, 33, 34, 37, 38, 41, 42, 44, 45), and 10 variants with unknown nationality (3,4,30). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old (1, 7-12, 14, 16-24, 26, 28, 29, 31-35, 38-42). ...
... De Laval et al. showed that upon exposure to ionizing radiation, TPO promotes C-NHEJ in stem and progenitor cell populations through binding to its receptor (MPL), thereby initiating MDS; however, this TPO/DNA-PK-mediated NHEJ repair pathway in HSC may be defective [116,117]. It was shown that downregulation of some NHEJ factors, such as Lig IV, Ku70, and Ku80, are involved in primary MDS [118]. Besides, the expression level of PARP1, an A-EJ factor, has been newly approved as a prognostic factor of MDS. ...
... According to a meta-analysis, the ABCB1 C1236T polymorphism is linked to an increased risk of imatinib resistance, but the ABCB1 G2677T and C3435T polymorphisms had no link to imatinib resistance (Zu et al. 2014). It is also found in a study that the SLCO1B3 334TT genotype shows association with a high risk of failure of cytogenic response and also revealed that the SLCO1B3 334GT/GG genotype is associated with cytogenetic response (Nair et al. 2017). The SLCO1B3 699GG and 344TT genotypes were shown to be strongly related to improved imatinib response in a Brazilian investigation (de Lima et al. 2015). ...
... Recurrent chromosomal aberrations associated with distinct clinical outcomes, continue to remain the most important prognostic factors for treatment planning in MDS. However, approximately 50% of MDS patients are cytogenetically normal suggesting the presence of distinct molecular events that contribute to disease phenotype and transformation 3,4 . ...