Leukaemia Flashcards
explain the key features of leukaemia
Leukemias are a diverse and complex group of hematologic malignancies characterized by the uncontrolled growth and accumulation of abnormal white blood cells in the bone marrow and, subsequently, in the blood. This condition is driven by genetic and epigenetic changes in hematopoietic stem cells and progenitors, which disrupt normal differentiation and self-renewal processes.
Key features of leukemia include:
Clonal Proliferation: Leukemias are characterized by the overproduction of immature, abnormal white blood cells derived from a single, genetically altered hematopoietic stem cell. These cells form a clonal population, meaning they are all descendants of a single abnormal cell.
Genetic and Epigenetic Events: The development of leukemia involves a series of genetic mutations and epigenetic alterations that accumulate in the affected cells. These mutations can vary widely between individuals and leukemia subtypes.
Loss of Differentiation: Leukemic cells often lose the ability to differentiate into mature blood cells. Instead, they remain in an immature, undifferentiated state, which can impair the production of normal blood cells.
Resistance to Apoptosis: Apoptosis is a process of programmed cell death that eliminates abnormal or damaged cells. Leukemic cells frequently evade apoptosis, leading to their uncontrolled growth.
Self-Renewal: Leukemic stem cells retain the capacity for self-renewal, which perpetuates the disease. This self-renewal ability contributes to the chronic nature of leukemia and the potential for relapse.
Defective Lineage Commitment: The genetic alterations in leukemia typically occur before the cells commit to a specific blood cell lineage (e.g., myeloid or lymphoid). This leads to the presence of undifferentiated and abnormal cells.
The term “leukemia” is derived from the Greek words “leukos” (meaning white) and “aima” (meaning blood). It reflects the historical observation that individuals with leukemia often have an excess of white blood cells in their blood counts.
explain the bone marrow and the lymphatic system
Bone Marrow:
Bone marrow is a soft and spongy tissue found inside the cavities of bones.
In adults, bone marrow is responsible for the production and maturation of blood cells. It plays a crucial role in hematopoiesis, which includes the formation of red blood cells, white blood cells, and platelets.
There are two main types of bone marrow: red marrow and yellow marrow. Red Marrow: Red marrow is primarily involved in blood cell production. It is found in certain bones, including the breastbone (sternum), skull, vertebrae, shoulder blades (scapulae), pelvis, ribs (flat bones), and contains significant amounts in the humerus (upper arm bone) and femur (thigh bone). Red marrow is essential for the generation of both red blood cells (erythropoiesis) and white blood cells (leukopoiesis).
Yellow Marrow: Yellow marrow is composed mostly of fat cells. It is found in the middle section of long bones. While yellow marrow does not actively produce blood cells, it can convert back to red marrow in certain situations, such as during severe anemia or in response to specific medical conditions.
Lymph System, Including the Spleen:
The lymphatic system is a network of vessels, nodes, and organs that plays a vital role in maintaining fluid balance, filtering harmful substances from the bloodstream, and supporting the immune system.
Key components of the lymphatic system include lymph nodes, lymphatic vessels, the thymus, and the spleen.
Spleen: The spleen is an organ located on the left side of the abdomen, just under the ribcage. It serves several functions, including:
Filtering and removing damaged or old blood cells from circulation.
Storing platelets, which are essential for blood clotting.
Participating in immune responses by producing lymphocytes (white blood cells). Acting as a blood reservoir, releasing stored blood in response to increased demand.
The spleen’s role in filtering blood and supporting the immune system makes it an essential component of the body’s defense against infections and diseases.
explain chromosomal translocation
The development of leukemia is indeed a complex and multistep process that involves the accumulation of genetic mutations over time. These mutations disrupt the normal control mechanisms for cell proliferation and differentiation, leading to the emergence of an autonomous and aberrant stem cell clone. One of the common genetic abnormalities observed in leukemia, as well as other cancers, is chromosomal translocation.
Chromosomal Translocation:
Chromosomal translocation is a type of genetic mutation in which a segment of one chromosome breaks off and attaches to another chromosome. This rearrangement can lead to the fusion of two different genes from the participating chromosomes.
In the context of leukemia, chromosomal translocations can result in the formation of fusion genes that encode abnormal proteins. These proteins may play a role in uncontrolled cell growth and survival.
Specific chromosomal translocations are associated with different subtypes of leukemia. For example, the Philadelphia chromosome (resulting from the translocation between chromosomes 9 and 22) is commonly found in chronic myeloid leukemia (CML).
These genetic abnormalities can be identified through cytogenetic testing, which examines the structure and number of chromosomes in a cell.
The accumulation of multiple genetic mutations, including chromosomal translocations, can transform normal hematopoietic stem cells into leukemic stem cells. Leukemic stem cells possess properties such as uncontrolled proliferation, reduced differentiation, and resistance to apoptosis (programmed cell death). They give rise to the clonal population of leukemia cells that dominate the bone marrow and blood, leading to the signs and symptoms of the disease.
explain chromosomal deletions
Chromosomal deletions are another type of genetic abnormality that can play a role in the development of leukemia, such as Acute Myeloid Leukemia (AML). A chromosomal deletion occurs when a segment of a chromosome is missing or deleted, which can result in the loss of specific genes. In the context of leukemia, chromosomal deletions can lead to the loss of genes that normally suppress the development of cancer or maintain proper cell growth control.
In AML, for example, certain chromosomal deletions or alterations can lead to the inactivation of tumor suppressor genes or the activation of oncogenes. These genetic changes disrupt the normal regulation of cell growth and differentiation, contributing to the uncontrolled proliferation of abnormal white blood cells characteristic of leukemia.
Different subtypes of AML can be associated with distinct chromosomal abnormalities, including deletions or mutations. These genetic alterations can be detected through cytogenetic testing, fluorescence in situ hybridization (FISH), or molecular genetic analysis.
explain chromosomal additions
Chromosomal additions, which often involve duplication of genetic material, are another type of chromosomal abnormality that can contribute to the development of certain diseases, including leukemia. An addition occurs when an extra segment of a chromosome is present, leading to an increase in the number of specific genes or gene sequences.
In the context of leukemia, chromosomal additions can result in genetic changes that promote abnormal cell proliferation and disrupt the regulation of blood cell development. These changes may lead to the activation of oncogenes or the inactivation of tumor suppressor genes, contributing to the transformation of normal hematopoietic cells into leukemic cells.
Chromosomal additions, like other genetic abnormalities, are often associated with specific subtypes of leukemia. The identification of these genetic alterations is essential for accurate diagnosis and classification of the disease. Various laboratory techniques, such as cytogenetic analysis and molecular genetic testing, can be used to detect chromosomal additions and other genetic abnormalities in leukemia cases.
explain submicroscopic mutations
Submicroscopic mutations involving changes in the base sequence of certain oncogenes are important drivers of cancer development, including leukemia. The RAS oncogene family is one of the most well-known oncogene families involved in various types of cancer, including acute myeloid leukemia (AML).
In AML, mutations in RAS genes are relatively common and are observed in approximately 50% of cases. These mutations often involve changes in the DNA sequence of RAS genes, such as KRAS, NRAS, or HRAS. When these mutations occur, they can lead to the activation of the RAS signaling pathway, which plays a critical role in regulating cell growth and proliferation.
The mutated RAS protein is constitutively active, meaning it continuously sends signals for cell division and growth, even when it is not needed. This uncontrolled signaling can result in the proliferation of leukemic cells and contribute to the development and progression of AML.
explain epigenetic changes
Epigenetic changes are alterations in gene expression or function that do not involve changes to the underlying DNA sequence. These changes can affect how genes are turned on or off, and they play a significant role in various diseases, including cancer, such as leukemia.
One common epigenetic modification is DNA methylation, which involves the addition of methyl groups to specific regions of the DNA molecule. In some cases, DNA hypermethylation can occur, leading to the silencing of genes that would normally act as tumor suppressors or regulators of cell growth. This epigenetic change can contribute to the development of cancer by allowing abnormal cells to evade normal growth control mechanisms.
In leukemia, including acute myeloid leukemia (AML), epigenetic changes are frequently observed. These changes can impact the expression of genes involved in hematopoiesis and cell differentiation, leading to the uncontrolled proliferation of leukemic cells.
Epigenetic therapies, such as the use of DNA demethylating agents or histone deacetylase inhibitors, have been developed to reverse abnormal epigenetic changes and restore the normal function of genes involved in the regulation of cell growth and differentiation. These treatments are a promising approach for some leukemia patients, as they aim to correct the underlying epigenetic alterations driving the disease.
explain how epigenetic myelation works
DNA Methylation: DNA methylation is an epigenetic modification that involves the addition of methyl groups to specific cytosine bases within a DNA molecule. This process can lead to changes in gene expression.
Gene Silencing: Hypermethylation of promoter regions in a gene can lead to gene silencing. When these promoter regions are heavily methylated, the gene is less likely to be transcribed into mRNA and ultimately translated into a functional protein.
Impact on Function: In the context of cancer, including leukemia, aberrant DNA methylation patterns can lead to the inactivation of tumor suppressor genes or the activation of oncogenes. This can disrupt the normal regulation of cell growth, differentiation, and apoptosis, contributing to the development and progression of the disease.
Therapeutic Implications: Understanding the epigenetic changes, like DNA methylation, that occur in leukemia and other cancers is critical for developing targeted therapies. DNA demethylating agents, histone deacetylase inhibitors, and other epigenetic-modifying drugs aim to reverse these abnormal epigenetic changes and restore normal gene function.
explain leukaemia
The description you provided is indicative of a pathological condition known as leukemia, which is a type of cancer affecting the blood and bone marrow. Leukemia results from the uncontrolled proliferation of immature and undifferentiated blood cells, often referred to as blast cells, in the bone marrow. These abnormal leukocytes can also infiltrate other organs, including the liver, spleen, and lymph nodes.
Leukemia is broadly classified into two main categories based on the type of blood cell affected: myeloid leukemia and lymphoid leukemia. In myeloid leukemia, there is uncontrolled proliferation of myeloid cells, such as granulocytes and monocytes, which can overcrowd the bone marrow, leading to reduced space for the development of lymphoid cells. As a result, white blood cell numbers may increase, leading to a decrease in other blood cell types, such as red blood cells and platelets.
In contrast, lymphoid leukemia involves the uncontrolled proliferation of lymphoid cells, which include lymphocytes. This can result in reduced red blood cell and platelet production, as well as other complications.
explain the risk factors associated with the development of leukemia
The factors you’ve listed are known risk factors associated with the development of leukemia, specifically myeloid leukemia (acute myeloid leukemia or AML). Here’s a brief explanation of each risk factor:
Exposure to Ionizing Radiations: High doses of ionizing radiation, such as those experienced during radiation therapy or nuclear accidents, can increase the risk of AML.
Previous Chemotherapy: Certain types of chemotherapy, while used to treat cancer, may be associated with an increased risk of developing secondary AML.
Occupational Chemical Exposure (e.g., Benzene): Prolonged exposure to chemicals like benzene, which is found in various industrial settings, has been linked to an increased risk of AML.
Genetically Determined Conditions (e.g., Down’s Syndrome): Genetic conditions like Down syndrome are associated with an elevated risk of AML and other forms of leukemia.
Viral Infection: In rare cases, infection with specific viruses, such as the human T-cell leukemia virus (HTLV-1), has been linked to the development of certain types of leukemia.
Myelodysplastic and Myeloproliferative Disorders: People with myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPNs) have a higher risk of developing AML.
Smoking: Smoking tobacco is a known risk factor for various cancers, including AML.
Preventive measures, such as reducing exposure to harmful chemicals and adopting a healthy lifestyle, can help lower the risk of developing leukemia. Early detection and prompt medical attention are crucial for better outcomes in leukemia cases.
explain the categorization of different types of leukemia
Acute Leukemias:
Acute Myeloid Leukemia (AML): AML is a fast-growing leukemia that primarily affects myeloid cells. It is characterized by the rapid proliferation of immature myeloid cells in the bone marrow and blood.
Acute Lymphoblastic Leukemia (ALL): ALL is another fast-growing leukemia, but it affects lymphoid cells. It is more common in children and is characterized by the rapid proliferation of immature lymphoid cells.
Chronic Leukemias:
Chronic Myeloid Leukemia (CML): CML is a slowly progressing leukemia that primarily affects myeloid cells. It is associated with a specific genetic abnormality known as the Philadelphia chromosome.
Chronic Lymphocytic Leukemia (CLL): CLL is a slow-growing leukemia that affects lymphoid cells. It is more common in older adults and is characterized by the accumulation of mature but abnormal lymphocytes.
Other Leukemias:
Hairy Cell Leukemia: Hairy cell leukemia is a rare, chronic leukemia that primarily affects B lymphocytes. The cells in this type of leukemia have a distinctive appearance.
Polycythemia Vera: Polycythemia vera is a myeloproliferative neoplasm that results in the overproduction of red blood cells.
T-Cell Leukemia/Lymphoma: T-cell leukemias and lymphomas are a group of rare malignancies that affect T lymphocytes. They can manifest as leukemia (in the blood and bone marrow) or lymphoma (in lymph nodes or other tissues).
explain the clinical manifestations that are common in acute myeloid leukemia (AML)
Neutropenia:
Neutropenia is a condition where there is a low count of neutrophils, a type of white blood cell that plays a crucial role in the immune system.
Manifestations include an increased risk of infections, especially serious or recurrent infections, as neutrophils are essential for fighting bacterial and fungal infections.
Common infections may become more severe, and even seemingly minor infections can lead to sepsis, a life-threatening condition.
Anemia:
Anemia is a condition characterized by a low red blood cell count and a reduced capacity to carry oxygen to tissues and organs.
Manifestations of anemia in AML patients include fatigue, weakness, pallor (paleness), and shortness of breath (SOB on exertion) due to a decreased oxygen-carrying capacity.
Some patients may also experience cold intolerance.
Thrombocytopenia:
Thrombocytopenia is a condition where there is a low platelet count in the blood.
Manifestations include a heightened risk of bleeding, which can lead to symptoms such as easy bruising, petechiae (small red or purple spots on the skin or mucous membranes), and, in severe cases, more significant bleeding, which may be an emergency situation.
explain the clinical manifestations that can occur in acute myeloid leukemia (AML)
Organomegaly:
Organomegaly refers to the enlargement of organs in the body. In AML, the most commonly affected organs are the liver, spleen, and lymph nodes.
The overgrowth of leukemia cells in the bone marrow and their spread into these organs can lead to their enlargement.
Enlarged organs may be palpable during a physical examination and can be confirmed through imaging studies like ultrasound, CT scans, or MRI.
Gum Hypertrophy:
Some patients with AML may experience gum hypertrophy, which is the abnormal enlargement of the gums.
This condition is attributed to the infiltration of leukemia cells into the gum tissue.
Bone Pain:
Bone pain is a common symptom in leukemia patients. The proliferation of leukemia cells in the bone marrow can lead to bone pain, particularly in the long bones and pelvic bones.
Bone pain may be described as a deep, aching pain.
Infiltration of Other Organs:
Leukemia cells can infiltrate other organs and tissues as well, leading to a variety of symptoms.
Central nervous system (CNS) involvement can result in neurological symptoms such as headaches, confusion, and seizures.
Skin involvement may lead to skin lesions or rashes.
Testicular involvement can cause testicular enlargement or discomfort.
These manifestations are related to the impact of leukemia cells on different body systems and organs. Organomegaly and gum hypertrophy are often visible on examination, while bone pain and other organ-specific symptoms can be sources of discomfort and concern for patients.
explain leukostasis
Leukostasis is a condition characterized by the accumulation of leukemic cells, such as white blood cells (leukocytes), in the microcirculation of the body. This accumulation can lead to various clinical complications. Here’s an explanation of the clinical manifestations associated with leukostasis:
Impaired Perfusion:
The accumulation of leukemic cells in the small blood vessels impairs the normal flow of blood, reducing perfusion to affected tissues and organs.
Impaired perfusion can lead to tissue ischemia (inadequate blood supply) and hypoxemia (low oxygen levels in the blood).
Hypoxemia:
Due to reduced oxygen delivery to tissues, leukostasis can result in hypoxemia, a condition where there is an insufficient amount of oxygen in the blood.
Symptoms of hypoxemia may include shortness of breath, difficulty breathing, and cyanosis (bluish discoloration of the skin and mucous membranes).
Stroke:
Leukostasis can lead to the formation of blood clots in small blood vessels, which can obstruct blood flow to the brain.
This can result in stroke, characterized by symptoms such as sudden weakness, numbness, confusion, difficulty speaking, and loss of coordination.
Fever and Sweats:
Leukostasis can trigger an inflammatory response, leading to fever and night sweats.
Priapism:
Priapism is a prolonged and painful erection of the penis that can occur as a complication of leukostasis. It is caused by the accumulation of leukemic cells in the blood vessels of the penis.
Myocardial Infarction (MI):
In some cases, leukostasis may lead to impaired blood flow to the heart, increasing the risk of myocardial infarction (heart attack).
Headaches:
Headaches can result from the reduced blood flow and oxygen supply to the brain caused by leukostasis.
Disseminated Intravascular Coagulation (DIC):
DIC is a serious medical condition where there is widespread activation of the blood clotting system.
Leukostasis can contribute to the development of DIC, which is associated with bleeding, clot formation, and organ dysfunction.
explain sternal tenderness
Sternal tenderness refers to pain or tenderness in the breastbone (sternum), which is located in the center of the chest. This symptom is not typically associated with acute lymphoblastic leukemia (ALL). Sternal tenderness is more commonly seen in conditions other than leukemia, such as musculoskeletal issues, chest wall injuries, infections, or inflammation of the sternum.
Acute lymphoblastic leukemia (ALL) is a type of blood cancer that primarily affects the white blood cells. While leukemia can cause a variety of symptoms, sternal tenderness is not a characteristic symptom of ALL. Common symptoms of ALL may include:
Fatigue
Weakness
Unexplained weight loss
Frequent infections
Bone pain or joint pain
Easy bruising or bleeding
Enlarged lymph nodes
Fever
Pale skin (anemia)
Abdominal pain or fullness (due to an enlarged spleen or liver)
