Author: Yu, Man Yee
Title: The potential of autophagy flux as prognostic and therapeutic marker of heterogeneous AML.
Advisors: Ma, Alvin (HTI)
Degree: M.Sc.
Year: 2022
Subject: Acute myeloid leukemia
Cell death
Hong Kong Polytechnic University -- Dissertations
Department: Department of Health Technology and Informatics
Pages: vii, 47 pages : color illustrations
Language: English
Abstract: Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by abnormal clonal hematopoietic progenitors. This means that the production of immature blast cells is uncontrolled in the peripheral blood and bone marrow, which leads to ineffective erythropoiesis and bone marrow failure. AML comprises approximately 80% of adult leukaemia cases.
Autophagy is a catabolic lysosomal degradation process. It has several functions that are important for cellular homeostasis and survival in the human body, such as housekeeping roles that remove the damaged organelles or cellular components; a host defence mechanism that kills the foreign invasive pathogens; and a role in cellular stress that helps to regulate the nutrient deprivation stress.
AML and autophagy are closely related because autophagy contains tumour suppressive and tumour promoting properties (White & DiPaola, 2009), pharmacological regulation of autophagy also differs in various AML subtypes. For tumour promoting properties, activation of autophagy by anti-leukemic drugs may act as a pro-survival response that contributes to AML leukemic stem cells (LSCs) drug resistance. For tumour suppressive properties, autophagy induction by available drugs may provide an anti-leukaemia effect to eliminate the oncoproteins.
Due to autophagy is a dynamic process that can have tumour promoting or tumour suppressive properties. If autophagy level can be a marker to monitor the progression of AML stage, it is helpful for AML treatment because controlling autophagy flux levels may affect the AML mechanism.
In the experiment result, flow cytometry, fluorescence microscopy, and RT-PCR were used to assess levels of autophagy in three AML cell lines, MV4-11, TMP-1, and MOLM-13 which are cell lines with different FLT3 mutations, were used. Midostaurin effectively increased the autophagy flux level in all AML cell lines with no affect normal cells. MV4-11 and TMP-1 showed the greatest increase following Midostaurin treatment.
Interestingly, RT-PCR revealed that treatment with a high Midostaurin concentration was associated with a proportionally high fold change in MV4-11 and MOLM-13 gene expression, but not in TMP-1. The overall gene expression of TMP-1 was the lowest among the three cell lines. Gene expression could distinguish between cells containing mutant and wild-type FLT3 in all cell lines; however, further investigation is required. Moreover, the result was limited to four specific AML cell lines and treatment with midostaurin. Therefore, further studies should be conducted, such as different cell lines and drugs for AML.
Rights: All rights reserved
Access: restricted access

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