I'm a Health Systems Manager by profession and currently a Clinician  in  Oncology department Pediatrics.
I cherish discipline, hard work, leading is my desire  and prosperity in Childhood cancer is my dream.
I am finalising  Masters in Public Health currently, my Thesis on in-depth analysis of Pediatric oncology building blocks.


Molecular characterization and biomarker identification in pediatric B-cell acute lymphoblastic leukemia.
 
Background:
B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Despite high cure rates, the management of B-ALL remains challenging due to its high heterogeneity and propensity for relapse. This study aimed to delineate molecular features of pediatric B-ALL and explore the clinical utility of circulating tumor DNA (ctDNA) as a biomarker in B-ALL. 
Objectives
Comprehensive Molecular Profiling:Identify recurrent and novel gene mutations, structural variations (like gene fusions)
Biomarker Discovery & Validation:Find novel diagnostic biomarkers (e.g., specific gene fusions, microRNAs) for early detection
Risk Stratification & Personalized Therapy:Refine molecular classification of B-ALL to better stratify patients into low, standard, and high-risk groups.
Disease Monitoring:Explore non-invasive monitoring using circulating tumor DNA (ctDNA) in blood (liquid biopsy) to track disease burden and MRD.
Understanding Pathogenesis:Uncover new biological pathways and therapeutic targets by linking genetic profiles to disease behavior and immune responses
Methods: 
The study analyzed 146 primary pediatric B-ALL patients who were diagnosed from August 2020 to April 2023 and received systemic chemotherapy in Kenya. Baseline bone marrow (BM) and plasma samples were collected for next-generation sequencing (NGS) to profile the mutational landscape. BM samples collected on day 30 of the treatment were utilized for minimal residual disease (MRD) testing to assess treatment efficacy. Transcriptomic profiling of baseline BM samples was performed via bulk RNA sequencing.
Results:
Transcriptomic analysis revealed that 86.3% of patients (126 out of 146) could be categorized into 13 distinct molecular subtypes, with hyperdiploidy emerging as the predominant subtype. Baseline BM NGS identified gene fusions in 61% of patients, including 37 novel fusions previously unreported in B-ALL.. Despite initially responding well to therapy, the patient experienced disease progression after a year, indicating a poor prognosis. Baseline plasma ctDNA, which exhibited high mutational concordance with paired baseline BM samples, also demonstrated significant associations with chemotherapy efficacy, highlighting its potential as a non-invasive tool for disease monitoring and treatment outcome prediction. 
Conclusions:
This study elucidated novel gene fusions and potential biomarkers for treatment response in pediatric B-ALL. Importantly, both baseline plasma ctDNA and BM samples offer promising prognostic insights into chemotherapy responses, paving the way for non-invasive monitoring strategies in the management of pediatric B-ALL.

MOLECULAR CHARACTERISATION