Research

Life Sciences & Biotechnology

Title :

Detection of novel genetic aberrations by exome sequencing and its association with clinical pathogenesis leading to chemotherapy resistance in chronic myeloid leukemia in adolescents and young adults.

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Priyavadhana Balasubramanian, All India Institute Of Medical Sciences (AIIMS), Rishikesh, Uttarakhand

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Adolescents and young adults (AYA) patients (15-39 years) with malignancy have unique features as they differ in prognosis, outcomes, treatment strategies and also possibly biology when compared to their older counterparts. There is presently very limited study on the biology or outcomes of Chronic Myeloid Leukemia (CML) in AYA. A study done by Pemmaraju et al studied 61 AYA patients with CML treated with Tyrosine Kinase inhibitors (TKIs) and concluded that these patients have a lower response rate to initial TKI therapy. The reasons for this lower response rate need further evaluation and it may be related to disease biology. This study aims at studying the novel genetic aberrations in CML AYA and associating these with response to TKI therapy. Objectives: 1.To study the novel genetic aberrations by exome sequencing in CML in AYA. 2. To associate these genetic aberrations with response to TKI therapy in CML in AYA. Methods: The study will be conducted prospectively in 50 patients of CML in AYA (15-39 Years) at two different time points (At diagnosis and at 12 months following therapy) for a duration of three years. The patient demographic details will be noted down at diagnosis from the patient case records. Complete blood counts, bone marrow examination findings, cytogenetics and RT- PCR findings, whichever tests being done routinely at diagnosis, 3 months, 6 months, 12 months will be collected. The participants who fulfill the inclusion criteria will be enrolled in the study and informed consent will be taken. There will be no extra sample taken from the patient. The peripheral blood or bone marrow done routinely at diagnosis and at 12 months will be used for whole-exome sequencing. The white cell pellet is extracted from the peripheral blood or bone marrow aspirate (2-3ml) collected in EDTA vacutainer on the same day and stored at -80 deg C. DNA library preparation will be made in batches from the frozen white cell pellets. The prepared libraries will be transported to the Institute Of Life Sciences and Biotechnology (Ils), Odisha, Bhubaneshwar for exome sequencing. The raw data will be provided to us for analysis. Expected outcome: This study is expected to identify novel aberrations and its association with clinical pathogenesis leading to chemotherapy resistance. Also, we can see the relationships of these genetic aberrations with patient response to TKIs.

Total Budget (INR):

43,91,332

Organizations involved