Molecular leveraging of HOX-embedded non-coding RNAs in the progression of acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by impaired differentiation of myeloid cells leading to hematopoietic failure. Despite advances, the molecular mechanisms driving AML remain incompletely understood, limiting the identification and targeting of critical vulnerabilities in leukemic cells. Homeobox (HOX) genes, encoding transcription factors essential for myeloid and lymphoid differentiation, are distributed across four clusters: HOXA (chromosome 7), HOXB (chromosome 17), HOXC (chromosome 12), and HOXD (chromosome 2).

The plasma EBV DNA load with IL-6 and VEGF levels as predictive and prognostic biomarker in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein-Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC.

Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature.

Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy.

Exosomal long non-coding RNA MALAT1: a candidate of liquid biopsy in monitoring of Wilms' tumor.

Purpose: Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication.

Expression of long non-coding RNA UCA1 and its clinical relevance in paediatric acute myeloid leukemia.

The underlying mechanisms and clinical significance of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is largely unknown in acute myeloid leukemia (AML). We aimed to study the expression of lncRNA UCA1, and its biological and clinical relevance in AML. Expression of lncRNA UCA1 was quantified in peripheral blood (PB) samples of children with AML (n=69), post-induction, after achieving complete remission (CR) (n=8), and in patients who had relapsed (n=10).

Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution.

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period.

Analysis of miR-375-3p, miR-197-3p, and miR-15a-5p Expression and Their Clinical Relevance as Biomarkers in Lung Cancer.

MicroRNAs (miRNAs) play an important regulatory role and serve as biomarkers in various human cancers. However, their role in the prognosis and predicting response to therapy in Indian lung cancer patients is not fully explored. We collected surgically resected tumors and paired adjacent normal lung tissues from 29 early-stage and tissue biopsies from 103 locally advanced and metastatic lung cancer patients in this prospective study.

Serial Evaluation of T cell Subsets in Paediatric Acute Myeloid Leukaemia- a Prospective Study.

Purpose: There is paucity of data regarding T-cells in paediatric AML patients. The aim of this prospective study was to evaluate trend of T-cell subset during disease course of paediatric AML patients and to see its correlation with patient characteristics and survival outcome.

Methods: T-cell subsets (CD3, CD4 and CD8) were evaluated by flow-cytometry at diagnosis, post-induction, post-treatment completion, at 3 months and 6 months post-treatment completion, and relapse in 29 pediatric AML patients.

Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients.

The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients.

Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer.

Small cell lung cancer (SCLC), a smoking-related highly aggressive neuroendocrine cancer, is characterized by rapid cell proliferation, early metastatic dissemination, and early relapse due to chemoresistance to first-line platinum-doublet chemotherapy. Genomically, SCLC tumors show nearly universal loss of TP53 and RB1 tumor suppressor genes, while gene expression signature classifies them into 4 distinct subgroups based on the expression patterns of lineage transcription factors - ASCL1/ASH1, NEUROD1, YAP-1, and POU2F3. Due to the lack of targetable molecular alterations and clinically useful diagnostic, prognostic and predictive biomarker, there is insignificant progress in the therapeutic management of SCLC patients.

Biological functions of long noncoding RNAs and circular RNAs in small-cell lung cancer.

We aim to discuss comprehensively the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in small-cell lung cancer (SCLC) biology and their clinical utility as cancer biomarkers. We searched the scientific literature to select articles related to the role of lncRNAs and circRNAs in SCLC biology or as cancer biomarkers. We identified that a number of lncRNAs and circRNAs can regulate key biological processes involved in SCLC development, including cell proliferation, metastasis and chemoresistance mainly acting as miRNA sponges.

Regulatory T cells in pediatric AML are associated with disease load and their serial assessment suggests role in leukemogenesis.

Background: Regulatory T cells (Tregs) modulate immune system by suppressing other immune cells. In current exploratory era of immunotherapy, the detailed enumeration data of Tregs cells in pediatric AML is lacking.

Aim: Serial assessment of Treg absolute values in pediatric AML at diagnosis and follow-up; and correlating with outcome.

Differential expression of circulating serum miR-1249-3p, miR-3195, and miR-3692-3p in non-small cell lung cancer.

Global deregulation in miRNA expression is a hallmark of cancer cell. An estimated 2300 mature miRNAs are encoded by human genome; role of many of which in carcinogenesis and as cancer biomarkers remains unexplored. In this study, we investigated the utility of miR-3692-3p, miR-3195, and miR-1249-3p as biomarkers in non-small cell lung cancer (NSCLC).

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.

Identification of differentially expressed circulating serum microRNA for the diagnosis and prognosis of Indian non-small cell lung cancer patients.

Purpose: Identification of noninvasive blood-based biomarkers is of utmost importance for the early diagnosis and predicting prognosis of advance stage lung cancer patients. MicroRNAs (miRNAs) has been implicated in numerous diseases, however, their role as diagnostic and prognostic biomarkers in Indian lung cancer patients has not been evaluated yet.

Methods: For the identification of differentially expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients, we performed small RNA sequencing.

Epigenetic regulators of programmed death-ligand 1 expression in human cancers.

The programmed cell death protein 1-programmed death-ligand 1 (PD-L1) axis has been successfully targeted in clinics and the use of immune check-point inhibitors have shown durable antitumor response in untreated or heavily treated advanced stage cancer. PD-L1 upregulation has been found to correlate with poor prognosis in multiple cancer types and expression of PD-L1 in intratumoral compartment has been suggested to influence immune response and act as a key determinant of checkpoint immunotherapy efficacy. Hence it becomes critical to understand the regulation of PD-L1 expression in cancer.

Aggressive serous epithelial ovarian cancer is potentially propagated by EpCAMCD45 phenotype.

Epithelial ovarian carcinoma (EOC) patients often acquire resistance against common chemotherapeutic drugs like paclitaxel and cisplatin. The mechanism responsible for the same is ambiguous. We have identified a putative drug-resistant tumour cell phenotype (EpCAMCD45) in the ascitic fluid of EOC patients, which appears to originate from the primary tumour.

High fms-like tyrosine kinase-3 (FLT3) receptor surface expression predicts poor outcome in internal tandem duplication (ITD) negative patients in adult acute myeloid leukaemia: A prospective pilot study from India.

Background & Objectives: Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome.

Hydrogen sulfide mitigates homocysteine-mediated pathological remodeling by inducing miR-133a in cardiomyocytes.

An elevated level of homocysteine called hyperhomocysteinemia (HHcy) is associated with pathological cardiac remodeling. Hydrogen sulfide (H2S) acts as a cardioprotective gas; however, the mechanism by which H2S mitigates homocysteine-mediated pathological remodeling in cardiomyocytes is unclear. We hypothesized that H2S ameliorates HHcy-mediated hypertrophy by inducing cardioprotective miR-133a in cardiomyocytes.

High receptor tyrosine kinase (FLT3, KIT) transcript versus anti-apoptotic (BCL2) transcript ratio independently predicts inferior outcome in pediatric acute myeloid leukemia.

Objective: In acute myeloid leukemia (AML), simultaneous expression of proliferative (FLT3, KIT) and anti-apoptotic genes (BCL2) is unknown. The aim of the study was to prospectively evaluate proliferative and anti-apoptotic gene transcripts, their interrelationship and impact on the outcome in pediatric AML patients.

Methods: We assessed proliferative and anti-apoptotic gene transcripts by Q-polymerase chain reaction (TaqMan probe) in 64 consecutive pediatric AML patients.

Relative receptor tyrosine kinases and anti-apoptotic transcripts hold potential for predicting inferior outcome in adult acute myeloid leukemia: a prospective pilot study.

Introduction: Acute myeloid leukemia is characterized by accumulation of immature cells because of imbalance between proliferation and apoptosis. In AML, simultaneous expression of proliferative (FLT-3, c-KIT) and antiapoptotic genes (BCL-2), are unknown.

Patients And Methods: We prospectively assessed proliferative and antiapoptotic gene transcripts using Taqman probe chemistry in 48 adult AML patients.

Quantitative assessment of BAX transcript and flow cytometric expression in acute myeloid leukemia: a prospective study.

Objective: Quantitative assessment of BAX transcripts and protein in acute myeloid leukemia (AML).

Methods: We quantitatively evaluated BAX gene transcripts by real-time polymerase chain reaction (TaqMan probe chemistry) and protein expression by flow cytometry.

Results: Consecutive 112 AML patients with a median age of 16 (1-59) years were recruited in the study.

FLT3-ITD mutation in relation to FLT3 expression in pediatric AML: a prospective study from India.

There is lack of data with regard to FLT3 expression in FLT3-ITD positive pediatric AML patients. Further, FLT3-ITD has not been systematically analyzed for outcome from Indian subcontinent. Amongst 64 consecutive pediatric AML patients, FLT3-ITD was present in 12 (19%) patients.