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    High TUBB2A expression in childhood T-ALL is correlated with the clinical outcome
    (Wiley, 2020) Khodzhaev, Khusan; Ng, Ozden Hatirnaz; Tugcu, Deniz; Erbilgin, Yucel; Ng, Yuk Yin; Celkan, Tiraje; Timur, Cetin
    Introduction Microtubules are polymers that perform functions such as mitosis, intracellular transport, cell morphology, and ciliary and flagellar motility. Since microtubules are taking active part in cell division, they are among direct targets of several antimitotic drugs. Methods Expression levels of tubulin isotypes were analyzed in microarray data of childhood diagnostic T-ALL samples (n = 31) and healthy thymocytes (n = 7). Findings were validated with qPCR in separate T-ALL cohort (n = 48), and clinical correlation analyses were performed.TUBB2A's effects were tested with siRNA-mediated knockdown in MOLT4 cell line, and apoptosis assay was carried out at 24, 48, and 72 hours time points. Results In microarray data,TUBB2Awas found to be the only differentially expressed tubulin isotype (adj.Pvalue = .01), which was validated by qPCR (P = .02). Samples representing differentiation stages of T cell showed an increasing trend ofTUBB2Atoward mature T-cell stage.TUBB2Aexpression was significantly higher in high-risk group patients (P = .026) and in a group with WBC counts >100 (x10(9)cells/L) (P = .029). HighTUBB2Awas also found to be a predictor of shorter OS (P = .029) and RFS (P = .042). Conclusion Aberrant expression of TUBB isotypes can affect the balance of microtubules or microtubule-associated proteins, which might lead to drug resistance/relapse. Contribution of cytoskeleton proteins to drug resistance needs further investigation, and understanding aberrant expression and mode of action of microtubules will improve therapy strategies.
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    Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect
    (Springer/Plenum Publishers, 2020) Khodzhaev, Khusan; Bay, Sema Buyukkapu; Kebudi, Rejin; Altindirek, Didem; Kaya, Aysenur; Erbilgin, Yucel; Ng, Ozden Hatirnaz
    Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missenseCD70variation was detected (NM_001252.5:c332C>T) in concordance withCD70phenotype and familial segregation was confirmed.CD70variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missenseCD70variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.