Leukemias: Types and Characteristics of Leukocytes
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Questions and Answers

How does flow cytometric immunophenotyping (FCI) aid in the diagnosis of Acute Lymphoblastic Leukemia (ALL)?

FCI helps diagnose ALL by identifying and classifying the specific immunophenotype of the cancerous lymphoblasts, distinguishing them from normal white blood cells and other types of leukemia.

What immunological mechanism underlies the ability of Natural Killer (NK) cells to target and destroy tumor cells?

NK cells identify and kill tumor cells by detecting changes or absence of MHC class I molecules on the surface of target cells, which indicates a compromised or infected state.

Explain the role of measurable residual disease (MRD) assessment in the management of Acute Lymphoblastic Leukemia (ALL).

MRD assessment helps to evaluate the effectiveness of treatment by detecting residual leukemic cells after initial therapy. Its presence indicates a higher risk of relapse, influencing decisions on further treatment intensification or alternative therapies.

How do cancerous lymphoblasts in Acute Lymphoblastic Leukemia (ALL) disrupt normal hematopoiesis and lead to common clinical manifestations?

<p>Cancerous lymphoblasts proliferate uncontrollably and crowd out normal hematopoietic cells in the bone marrow, leading to decreased production of functional blood cells. This results in anemia, increased risk of infection, and bleeding tendencies, causing symptoms like fatigue, fever, and easy bruising.</p> Signup and view all the answers

Describe the distinct functions of cytotoxic T cells and helper T cells in adaptive immunity, and how these roles are relevant to understanding immune responses in leukemia.

<p>Cytotoxic T cells directly kill infected or cancerous cells by releasing cytotoxic granules containing enzymes. Helper T cells secrete cytokines that activate other immune cells, enhancing both cell-mediated and humoral immune responses. In leukemia, cytotoxic T cells may target leukemic cells, while helper T cells support the overall immune response against the malignancy.</p> Signup and view all the answers

What are the key differences in the mechanisms by which B cells and T cells recognize and respond to antigens, and how do these differences contribute to their respective roles in adaptive immunity?

<p>B cells recognize antigens directly through their surface immunoglobulin receptors, leading to antibody production that neutralizes pathogens. T cells, on the other hand, recognize antigens presented by antigen-presenting cells (APCs) via MHC molecules, activating cell-mediated immunity. This difference allows B cells to target extracellular pathogens, while T cells target intracellular threats.</p> Signup and view all the answers

Explain the role of interferons in activating Natural Killer (NK) cells, and how this activation contributes to the innate immune response against tumors and infected cells.

<p>Interferons are cytokines that activate NK cells by increasing their cytotoxic activity and enhancing their ability to recognize and kill target cells. This activation strengthens the innate immune response against tumors and infected cells, as NK cells can then release cytotoxic granules containing enzymes that induce apoptosis in the target cells.</p> Signup and view all the answers

Distinguish between the roles of tumor lysis syndrome and central nervous system (CNS) involvement as complications in Acute Lymphoblastic Leukemia (ALL), highlighting their respective pathogeneses and clinical implications.

<p>Tumor lysis syndrome results from the rapid breakdown of leukemic cells, releasing intracellular contents that can cause metabolic abnormalities like hyperkalemia and renal failure. CNS involvement occurs when leukemic cells infiltrate the brain and spinal cord, leading to neurological symptoms. Tumor lysis syndrome is a metabolic emergency, while CNS involvement requires specific intrathecal chemotherapy to prevent relapse.</p> Signup and view all the answers

Explain the role of chemotaxis in neutrophil function and give two specific examples of chemoattractants involved in this process.

<p>Chemotaxis guides neutrophils to sites of damage or infection through chemical signals. Two chemoattractants are IL-8 and Leukotriene B4.</p> Signup and view all the answers

How do eosinophils contribute to allergic reactions, and what specific mechanisms do they employ in this process?

<p>Eosinophils contribute to allergic reactions through degranulation, releasing chemical mediators like histamine and proteins that cause inflammation and allergic symptoms.</p> Signup and view all the answers

Describe the functional significance of basophils carrying receptors for IgE, and what downstream effects does IgE activation trigger in these cells?

<p>IgE activation in basophils leads to the release of histamine, which causes vasodilation and amplifies the innate immune response.</p> Signup and view all the answers

How does the function of a monocyte change as it differentiates into a macrophage, and what is the significance of this transformation for immune responses?

<p>Monocytes differentiate into macrophages, enhancing their capacity for phagocytosis and antigen presentation, which is crucial for initiating and coordinating immune responses.</p> Signup and view all the answers

In the context of a complete blood count (CBC) report, what does a 'shift to the left' indicate, and what implications does this have for patient diagnosis?

<p>A 'shift to the left' indicates an increase in immature neutrophils (bands), suggesting an active acute infection or inflammatory process.</p> Signup and view all the answers

How do perforin and granzyme contribute to neutrophil function?

<p>Perforin and granzyme are used by neutrophils to induce apoptosis in target cells by punching holes in their cell membrane.</p> Signup and view all the answers

Differentiate between segmented neutrophils (segs) and banded neutrophils (bands) in terms of maturity and clinical significance.

<p>Segs are mature neutrophils with multi-lobed nuclei, while bands are immature neutrophils with a horseshoe-shaped nucleus; an increase in bands often indicates acute infection.</p> Signup and view all the answers

Explain how the location of eosinophils in different tissues can be indicative of various pathological conditions.

<p>Eosinophils found in tissues like the lung, skin, esophagus or internal organs suggest parasitic infection or allergic disease.</p> Signup and view all the answers

Discuss the role of TLRs (Toll-like receptors) in the activation of basophils and the subsequent immune responses triggered by this activation.

<p>TLRs on basophils recognize pathogens, leading to degranulation and release of inflammatory mediators like histamine which amplifies the innate immune response.</p> Signup and view all the answers

Explain the process and significance of monocyte storage in the red pulp of the spleen (Cords of Billroth).

<p>Monocytes are stored in the red pulp (Cords of Billroth) of the spleen as a reserve to replenish macrophages during inflammation, to help with viral or chronic infections, or when macrophage numbers are low.</p> Signup and view all the answers

In acute lymphoblastic leukemia (ALL), what is the significance of identifying specific chromosomal translocations during fetal hematopoiesis in the context of disease development and risk?

<p>Chromosomal translocations during fetal hematopoiesis can initiate leukemic transformation, predisposing individuals to ALL and indicating high-risk disease features.</p> Signup and view all the answers

How does the clinical presentation of B-cell chronic lymphocytic leukemia (CLL) differ when the disease manifests primarily as small lymphocytic lymphoma (SLL)?

<p>In SLL, the disease primarily involves lymph nodes, whereas CLL involves both lymph nodes and the peripheral blood with a higher B-cell count.</p> Signup and view all the answers

Explain the role of Fluorescent In Situ Hybridization (FISH) in the diagnosis and management of CLL, specifically focusing on the clinical implications of del(11q) and del(17p).

<p>FISH detects genetic abnormalities guiding prognosis and treatment. Del(11q) indicates more lymphadenopathy and poorer chemotherapy response. Del(17p) indicates advanced disease and resistance to chemotherapy.</p> Signup and view all the answers

In the context of acute myeloid leukemia (AML), how does the presence or absence of myeloperoxidase (MPO) within myeloblasts influence diagnostic and treatment strategies?

<p>The presence of (MPO) helps confirm the diagnosis of AML and is a criterion that is needed for differentiating AML from acute leukemias of lymphoid origin. MPO-positive AML may respond differently to specific chemotherapeutic agents.</p> Signup and view all the answers

What is the rationale behind using 'CNS prophylaxis' as part of the frontline therapy for acute lymphoblastic leukemia (ALL)?

<p>CNS prophylaxis is used to prevent leukemic cells from infiltrating the central nervous system, as the CNS is a sanctuary site where chemotherapy penetration is limited.</p> Signup and view all the answers

How do genetic factors and environmental exposures interact to increase the risk of developing B-cell chronic lymphocytic leukemia (CLL)?

<p>Genetic factors predispose individuals to CLL, while exposures like viral infections or chemicals may trigger or accelerate disease development in susceptible individuals.</p> Signup and view all the answers

Describe the significance of assessing 'risk stratification' in acute myeloid leukemia (AML) following initial diagnosis, and provide examples of factors that contribute to this assessment.

<p>Risk stratification guides prognosis, management, and therapy. Factors include cytogenetics, molecular mutations (e.g., <em>FLT3</em>, <em>NPM1</em>), age, and performance status.</p> Signup and view all the answers

Explain why 'smudge cells' are considered a characteristic finding in B-cell chronic lymphocytic leukemia (CLL) and how they are formed during the preparation of blood smears.

<p>Smudge cells are fragile lymphocytes that rupture during blood smear preparation. Their presence is characteristic of CLL due to the inherent fragility of CLL cells.</p> Signup and view all the answers

What are the key differences in cellular morphology and cytochemical staining patterns between myeloblasts in acute myeloid leukemia (AML) and lymphoblasts in acute lymphoblastic leukemia (ALL)?

<p>AML myeloblasts have Auer rods &amp; stain positive for myeloperoxidase (MPO). ALL lymphoblasts lack Auer rods &amp; typically stain positive for terminal deoxynucleotidyl transferase (TdT).</p> Signup and view all the answers

Explain the potential role of allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia (ALL) who exhibit high-risk features, and why this approach may be considered over other treatment modalities.

<p>HSCT can provide curative potential by replacing the patient's immune system with a donor's cells. This can eliminate leukemic cells and establish long-term remission in high-risk ALL.</p> Signup and view all the answers

Describe neutrophils?

<p>most common white blood cell, they are neutral pink and multi lobed with 2-5 lobes. They function in innate immune system and do phagocytosis and degranulation. They mainly are located in the skin &amp; mucous membrane and they life for a few hours to a few days. They respond to inflammation and bacteria and fungi. They go to blood vessels and intersistial tissue.</p> Signup and view all the answers

Describe eosinophils?

<p>make up 1-6% of white blood cells. They are red and bi-lobed. They function in degranulation. Releasing enzymes and growth factors as well as cytokines and life for a few days. They respond to parasites, allergic reactions. They are located in the thymus, GI tract, an spleen. They defend by degranulation</p> Signup and view all the answers

Describe basophils?

<p>least common white blood cell. They are either bi or tri lobed. They function in degranulation, releasing histamine, enzymes, and cytokines. They respond to allergic reactions, inflammatory reactions. They are located in small numbers in the blood vessels. They defend by releasing heparin and histamine.</p> Signup and view all the answers

Describe monocytes?

<p>They are in small amount and they are agranulocytes. They are kidney shaped and the largest white blood cell as well as being unilobar. They function in turning into macrophages and dendritic cells. They are stored in the spleen and they are made in the bone marrow. They respond in inflammation.</p> Signup and view all the answers

Describe lymphocytes?

<p>Any white blood cell in vertebrae immune system and there’s 3 types. Tell which function in cell mediated immunity. B cell function in humoral and antibody immunity. And natural killer cells which release cytotoxic granules and they react to tumors and infected cells no fining charges in the cell surface of the molecule.</p> Signup and view all the answers

What is acute lymphoblastic leukemia (ALL)?

<p>characterized by the overproduction of lymphoblastic in bone marrow, blood, tissue and they multiply. It has lymphoblasts that are immature white blood cells that stop the production of other cells. It causes less functional cells, increase risk for infection, fever, night sweats, and swollen lymph nodes. It also leads to abnormal masses</p> Signup and view all the answers

What is Measurable Residual Disease (MRD)?

<p>residual leukemia blasts are detected after chemotherapy despite there being less than 5% of blasts in the bone marrow.</p> Signup and view all the answers

Describe B-cell chronic lymphocytic leukemia (CLL)?

<p>It is the most common leukemia in adults that has an effect of B cell lymphocytes since they grow out of control and they stay in bone marrow and the blood. It causes high number of white blood cells, anemia, and swollen lymph nodes. It is diagnosed hen there is more than 5000 micro liters of B cells in peripheral blood with cytometry,</p> Signup and view all the answers

Acute myeloid leukemia (AML)?

<p>It is a cancer of myeloid line of blood cells and it is the most common acute leukemia. It is characterized by the growth of abnormal bite blood cells and it stays in the marrow, it also stops the production of other cells. It is inherited in the heterogenous group with clonal proliferation of myeloid blasts. it is diagnosed when there is more that 20% of myeloid blasts in bone marrow or peripheral blood. It has immature myeoblasts and many nuclei with a linear Auer rods.</p> Signup and view all the answers

what is acute promyelocytic leukemia (APL)?

<p>is is a subtype of AML that is caused by a translocation between of RARAa and chromosome 17, and PML on chromosome 15. It causes bleeding disorders from DIC and fibrinal lysis. It is treated with ATRA and arsenic and trioxide (ATO)</p> Signup and view all the answers

Chronic Myeloid Leukemia (CML)?

<p>It is characterized by increased and unregulated growth of myeloid cells in bone marrow that are mature but they stay in the bloood. It is a clonal bone marrow stem cell disorder and it causes proliferation of mature granuloycytes. It is caused by the translocation of the philade[hia chromosome which is a translocation between chromosomes 9 &amp; 22 that results in a BCR_ABLI. It is treated with TKI drugs</p> Signup and view all the answers

(FISH) FLuorescent in situ hybridization?

<p>It is a detected molecular abnormalities and it rese,nobles mature lymphocytes and it causes smudge cells. It includes del (11q) and del (17q)</p> Signup and view all the answers

Flashcards

T cell

A type of white blood cell involved in the adaptive immune response, with roles in cell-mediated immunity.

Helper T cell

A subtype of T cell that produces cytokines to enhance the immune response.

Cytotoxic T cell

A type of T cell that releases toxins to kill infected or cancerous cells.

B cell

A type of white blood cell that produces antibodies to neutralize foreign objects.

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Natural Killer Cells (NK)

Innate immune cells that kill infected or tumor cells by releasing cytotoxic granules.

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Acute Lymphoblastic Leukemia (ALL)

A cancer characterized by overproduction of lymphoblasts in children, affecting blood and bone marrow.

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Measurable Residual Disease (MRD)

Residual leukemic cells detected after treatment, indicating possible remaining disease.

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Lymphoblast

Immature white blood cells that are cancerous and impact production of other cells.

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Frontline Therapy

Includes induction, consolidation, maintenance, and CNS prophylaxis in treatment.

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B-cell Chronic Lymphocytic Leukemia (CLL)

Most common leukemia in adults affecting B-cell lymphocytes, leading to uncontrolled growth.

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Symptoms of CLL

High WBC count, swollen lymph nodes, anemia, infections, and weight loss.

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Diagnosis of CLL

More than 5000 B cells per microliter blood; cytometry shows less than 55% prolymphocytes.

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Fluorescent in situ hybridization (FISH)

Technique to detect molecular abnormalities in CLL; identifies chromosomal deletions.

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Acute Myeloid Leukemia (AML)

A rapidly progressing cancer of the myeloid lineage of blood cells.

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Symptoms of AML

Causes fatigue, infection risk, easy bleeding, and reduced RBC/WBC/platelet counts.

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Diagnosis of AML

Requires 20% or more myeloid blasts in blood or bone marrow.

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Acute Promyelocytic Leukemia (APL)

A subtype of AML characterized by specific genetic mutations.

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Myeloid Sarcoma

A mass in extramedullary tissues that reveals the presence of AML.

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Leukocytes

White blood cells (WBC) that defend the body in the immune system.

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Hematopoietic Stem Cell

Multipotent cell in bone marrow that produces WBC.

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Leukocytosis

Condition where the number of WBC is above normal.

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Leukopenia

Condition where the number of WBC is below normal.

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Granulocytes

Type of leukocyte with visible cytoplasmic granules, including neutrophils, eosinophils, and basophils.

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Neutrophil

Most common type of WBC (40-75%) that responds to inflammation and infections.

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Eosinophil

WBC (1-6%) involved in responses to parasites and allergic reactions.

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Basophil

Least common WBC (<1%) that releases histamine and is involved in allergic reactions.

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Monocyte

Large WBC (2-6%) that can differentiate into macrophages and dendritic cells.

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Lymphocyte

Type of WBC that is essential for the adaptive immune response, mainly found in lymph.

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Study Notes

Leukemias

  • Leukemias are cancers of white blood cells (WBCs) or leukocytes
  • WBCs are part of the immune system and are primarily found in blood and lymphatic systems
  • WBC count (WBC#): 4-11 x 109/L (microliters)
  • Leukocytosis: WBC count above normal
  • Leukopenia: WBC count below normal

Types of Leukocytes

  • Granulocytes: contain visible cytoplasmic granules

    • Neutrophils (40-75%): most common WBC, multi-lobed, stain neutral pink, phagocytic, fight infection, short lifespan
    • Eosinophils (1-6%): stain red, bilobed, respond to parasites and allergic reactions, have enzymes to fight parasites
    • Basophils (<1%): stain dark blue, release histamine and other chemicals involved in inflammatory response
  • Agranulocytes: do not contain visible granules

    • Monocytes (2-8%): largest WBC, kidney shaped, become macrophages, important in phagocytosis
    • Lymphocytes (20-40%): diverse functions in immune response, including cell-mediated immunity. T cells, B cells, and Natural Killer (NK) cells.

Specific Leukemias

  • Acute Lymphoblastic Leukemia (ALL): Overproduction of immature lymphocytes (lymphoblasts)
  • Chronic Lymphocytic Leukemia (CLL): Most common leukemia in adults, affects B cells. Characterized by buildup of mature lymphocytes and often has a later onset
  • Acute Myeloid Leukemia (AML): Cancer affecting myeloid cells; rapid growth of abnormal myeloblasts in bone marrow, preventing normal blood cell production
  • Chronic Myeloid Leukemia (CML): Unregulated growth of myeloid cells in the bone marrow, resulting in an accumulation of mature granulocytes in blood and has a specific chromosomal translocation.
  • Myelodysplastic Syndromes (MDS): Ineffective hematopoiesis (blood cell production) that involves the bone marrow. Risk of transforming into acute leukemia.

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Description

Leukemias are cancers of white blood cells. White blood cells are part of the immune system and are primarily found in blood and lymphatic systems. There are two main types of leukocytes: granulocytes and agranulocytes.

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