Date of Award

11-11-2023

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Fareena Bilwani

Second Advisor

Dr. Bushra Moiz

Third Advisor

Dr. Anila Rashid

Department

Biological and Biomedical Sciences

Abstract

Acute myeloid leukemia (AML) is a rare hematological malignancy that commonly affects the elderly population with low 5-year overall disease-free survival. The treatment of AML has remained a challenge due to genetic and cytogenetic heterogeneity which increase the likelihood of relapse. New therapeutic options such as cellular immunotherapy are now evolving including the use of allogeneic NK cells.
Objective: This study aimed to investigate the expression pattern of CD112, CD155, and MICA/B in AML patients harboring various genetics and cytogenetic abnormalities. Methods: The expression of CD112, CD155, and MICA/B was analyzed on four different subsets of AML cells by flow cytometry. The expression of ligands was quantified as the number of cells per 106 within each population along with the surface level of ligand per cell as the relative mean fluorescence intensity (RMFI).
Results: It was found that the number of cells expressing CD112, CD155, and MICA/B was low in the early progenitor/LSC population in most AML cases compared to the more differentiated blasts and late progenitor cells. In contrast, the RMFI of CD112, CD155, and MICA/B was high in most cases of AML on all four cell populations irrespective of the hematopoietic differentiation stage. In the blasts and late progenitor populations, the number of cells expressing CD112, CD155, and MICA/B was high in AML cases harboring t(15;17) (q22;q12), trisomy 11 and no cytogenetic abnormality. AML cases harboring t(15:17) (q22;q12) showed an increased expression of CD112 and MICA/B in the early progenitor/LSC population. In AML cases harboring t(15:17)(q22;q12), monosomy 7, mutation in NPM1 with FLT3-ITD, and blastic plasmacytoid dendritic cell tumour and AML with no cytogenetic abnormality showed increased RMFI of CD112, CD155, and MICA/B in differentiated blasts-, late- and early-progenitor AML cells. Moreover, AML cases with t(15:17) (q22;q12) and no cytogenetic abnormality revealed increased expression and RMFI of CD112, CD155, and MICA/B on blast and late progenitor cells.
Conclusion: The results show that the expression of CD112, CD155, and MICA/B is not consistent across all cases of AML. This suggests that allogeneic NK cell-based immunotherapy needs to be tailored in patients diagnosed with AML depending on its expression on blasts and late progenitor versus early progenitor cells.

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Last Page

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