Topic Abstract: Leukemia – how our genes make (or break) the blood

Olga Guryanova, M.D., Ph.D.

Assistant Professor, Department of Pharmacology & Therapeutics

Presentation Title: Epigenetics of Leukemia

By producing over 2 million new mature blood cells every second, the bone marrow, which is the home of the hematopoietic system, is the hardest working organ in the human body. Normal blood production starts with the hematopoietic stem cells (HSCs), specialized cells in the bone marrow that make mature cells of the blood in the process called differentiation. At the same time, these stem cells need to replenish themselves to maintain life-long blood production, in the process called self-renewal. Imbalance between differentiation and self-renewal is the root cause of diseases such as acute myeloid leukemia (AML) and other blood cancers. AML is characterized by inefficient blood production with progressive anemia (low numbers of red blood cells) and loss of normal mature white blood cells and platelets in the circulation that are being replaced by pernicious leukemic blasts. Blood production by HSCs is maintained by many specialized genes being switched on and off in a timely and coordinated manner. If something goes awry in this process, it can lead to disease such as leukemia. Over time, mutations, or errors, accumulate in the DNA, and some of the important genes may become broken. As the result, this sets the blood stem cells on the path to becoming leukemic. At the same time, each “differentiation” and “self-renewal” gene needs to be activated or shut down in a precise order in time. Akin to bookmarks, molecular tags are placed to mark genes that are active or silent without changing their DNA sequence, called “epigenetic regulation.” If proper epigenetic regulation is lost, it can lead to some genes being incorrectly marked for activation or not red-flagged for shutoff, disturbing the balance between self-renewal and differentiation, corrupting blood production, and contributing to leukemia development.

Dr. Olga Guryanova is a cancer biologist at the UF Health Cancer Center. Her lab studies the epigenetic (or gene regulation) mechanisms that sustain normal blood production and what can go haywire leading to premalignant changes in the HSCs and ultimately to acute myeloid leukemia. Her team use this molecular knowledge to develop better therapies for this deadly disease and to improve the lives of leukemia patients.

Core Standards

SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and pathogenic agents to health from the perspectives of both individual and public health

SC.912.L.14.12 Describe the anatomy and histology of bone tissue.

SC.912.L.14.34 Describe the composition and physiology of blood, including that of the plasma and the formed elements.

SC.912.L.14.In.a Identify that all living things are made of cells and cells function in similar ways (cell theory).

SC.912.L.16.8 Explain the relationship between mutation, cell cycle, and uncontrolled cell growth potentially resulting in cancer.

SC.912.L.16.9 Explain how and why the genetic code is universal and is common to almost all organisms.

SC.912.N.2.4 Explain that scientific knowledge is both durable and robust and open to change. Scientific knowledge can change because it is often examined and re-examined by new investigations and scientific argumentation. Because of these frequent examinations, scientific knowledge becomes stronger, leading to its durability.

SC.912.N.2.5 Describe instances in which scientists’ varied backgrounds, talents, interests, and goals influence the inferences and thus the explanations that they make about observations of natural phenomena and describe that competing interpretations (explanations) of scientists are a strength of science as they are a source of new, testable ideas that have the potential to add new evidence to support one or another of the explanations.

SC.912.N.1.6 Describe how scientific inferences are drawn from scientific observations and provide examples from the content being studied.

SC.912.N.1.3 Recognize that the strength or usefulness of a scientific claim is evaluated through scientific argumentation, which depends on critical and logical thinking, and the active consideration of alternative scientific explanations to explain the data presented.

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