Acute Myeloid Leukemia and Cardiotoxicity

By: Elizabeth Zee ‘25 STEM In The

In recent decades, cancer research has progressed from the question of what caused their death to how to prevent it. Even though technology has improved and the knowledge of cancer has increased, the unfortunate answer is that as of current progress, there is no preventing cancer Whether you’re an office worker, a secretary, or the very scientist studying cancer, there is always a risk that you, too, could get it

Oncology is a field where the diseases scientists study differ from person to person, and a drug effective for patient A might not necessarily work for patient B. However, because of this, scientists working on drugs and cures for cancer are given more grants leading to more breakthroughs year after year Today, there is hope at every stage of cancer, with new drugs that work effectively even against stage 4 cancer cells But what happens when the spread of cancer lies undetected until it is too late and the spread is too aggressive to handle? This case study will focus on the treatments of acute myeloid leukemia and the aftereffects of its treatment

Leukemia is a broad term used to describe the cancer of the body’s blood-forming tissues, especially the bone marrow and the lymphatic system. Acute myeloid leukemia (AML), also known as acute myelogenous cancer or acute nonlymphocytic leukemia, is an aggressive form of leukemia AML progresses rapidly due to its origins in the bone marrow, which affects the production of unmutated white blood cells, red blood cells, and platelets This results in recurrent infections because of mutated white blood cells, and easy bruising due to the lack of platelets. The most common treatment of AML is chemotherapy, which is the use of cytotoxic drugs to help kill off the rapidly growing cells.

Over time, chemotherapy can become less effective, especially in older patients whose leukemic cells become more resistant to standard chemotherapy Because older patients are more susceptible to diseases, they are not compatible with myelosuppressive chemotherapy (the reduction of white blood cell population) as it yields a 25% mortality rate (4). Therefore, the best action for older patients is to use cytotoxic drugs that specifically target the cancerous cells

This brings us to Doxorubicin, the most commonly used drug specific to AML, although it has been used to treat a variety of other cancers as well. Doxorubicin is an antibiotic derived from the Streptomyces peucetius bacterium and is part of an anthracycline group of chemotherapeutic agents. The issue that lies in Doxorubicin is its extremely cardiotoxic nature as discussed in the study titled “Doxorubicin Cardiotoxicity May Be Caused by Its Metabolite, Doxorubicinol”, where researchers broke down and tried and separate the toxicity from the drug. This study focuses on what makes Doxorubicin so cardiotoxic and opens the floor to other researchers who want to try and inhibit doxorubicinol to reduce the drug’s cardiotoxicity (1) Doxorubicin has been used since the 1960s simply because it is so aggressive towards all cells in the human bo

This is not to say that there is no hope for a safer way to stop AML in the field of oncology. Researchers are constantly searching and working on how to make therapies less cardiotoxic. Whether that be studying the genes that help improve resistance to cardiotoxicity as shown in the study titled, “p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities” (2). Or getting to the root itself with the study called “Uncoupling DNA damage from chromatin damage to detoxify doxorubicin” (3).

There is so much hope for the field of oncology and many researchers are making headway into the field with their discoveries. With the rate at which scientific papers and research are being produced, it’s safe to say that in terms of curing cancer, researchers are making progress, slowly but steadily One day, we can finally say that prevention is better than cure when speaking about cancer but for now, we have to wade through the questions about cardiotoxicity and walk to our solution.

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Olson R D Mushlin P S Brenner D E Fleischer S Cusack B J Chang B K & Boucek R J (1988) Doxorubicin cardiotoxicity may be caused by its metabolite doxorubicinol Proceedings of the National Academy of Sciences 85(10) 3585–3589 https://doiorg/101073/pnas85103585

Li, J, Wang, P, Long, N A, Zhuang, J, Springer, D A, Zou, J, Lin, Y, Bleck, C K E, Park, J-H, Kang, J-G, & Hwang, P M (2019) p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities Proceedings of the National Academy of Sciences of the United States of America, 116(39), 19626–19634 https://doiorg/101073/pnas190497911

Flores, I Q, & Ershler, W (2010, February) Managing neutropenia in older patients with cancer receiving chemotherapy in a community setting Clinical journal of oncology nursing https://doiorg/101188/10CJON81-86

Science Photo Library (nd) Acute myeloid leukaemia micrograph - stock imageC013/7012 Science Photo Library https://wwwsciencephotocom/media/467688/view/acutemyeloid-leukaemia-micrograph