Chronic Leukemias (Lymphoproliferative and Myeloproliferative Disorders) Flashcards
Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) differ only in ______ ______ involvement. If blood lymphocyte count is ______ than 5000, the cancer is classified as ______. ______ is the most common leukemia in the Western World.
Peripheral blood; greater; CLL; CLL
Pathogenesis of CLL and SLL (4)
- Indolent, slow growing tumor cells more focused on survival than proliferation
- Contain high levels of BCL2, which inhibit apoptosis
- Express signals through B cell receptor that flow through the Bruton Kinase (BTK), which contribute to expression of genes that promote survival
- Can cause immune dysregulation, especially in B cells: the accumulation of CLL/SLL suppresses B cell function leading to hypogammaglobulinemia. This can result in autoantibodies against RBC and platelets made from non-malignant B cells due to impaired immune tolerance.
Characteristics of CLL and SLL morphology (6)
- Smudge cells: lymphocytosis of small, mature-appearing lymphs that smudge on peripheral blood smear due to fragility
- Lymph nodes characteristic of small lymphocytes: dark, round nuclei and scant cytoplasm
- Proliferation centers are characteristically the foci of mitotic cells
- Bone marrow, spleen, and liver are involved in nearly all cases
- 50% have karyotypic abnormalities: most common trisomy involvement is at chromosome 12 and most common deletions are chromosomes 11, 13, and 17
- Chromosome translocations are rare, unlike many other B cell neoplasms
B cell markers of CLL and SLL
CD20, CD5, and Ig’s
Clinical features of CLL and SLL (9)
- Initially asymptomatic
- Most common symptoms are nonspecific, such as fatigue, weight loss, and anorexia
- 50-60% of patients present with generalized lymphadenopathy, hepatosplenomegaly, and hypogammaglobulinemia (increased susceptibility to infection)
- Less commonly, autoimmune hemolytic anemia and thrombocytopenia are seen
- In SLL, WBC is increased slightly or can exceed 200,000 cells/microliter
- The presence of TP53 is associated to a less than 30% survival rate
- Abnormalities of chromosome 13q equates to the same survival rate as the general disease presentation
- A small fraction of aggressive tumors (resembling DLBCL) have a median survival rate of less than 1 year
- Cured via hematopoietic stem cell transplantation, which is reserved for young patients that failed conventional therapy
What is HCL?
Hairy Cell Leukemia
HCL is an ______ indolent B cell neoplasm characterized by the presence of ______, ______-______ cytoplasmic projections.
Uncommon; fine, hair-like
All cases of HCL are associated with mutations in the ______/______ kinase, ______.
Serine/threonine; BRAF
B cell markers of HCL
CD20, surface immunoglobin, CD11c (unique), and CD103 (unique)
Clinical features of HCL (7)
- Occurs in older males
- Manifestations include infiltration of the bone marrow and spleen
- Splenomegaly (most common finding), pancytopenia (marrow infiltration and splenic sequestration), leukocytosis
- If untreated, pancytopenia and infections are the two most major problems.
- HCL is extremely sensitive to chemotherapeutic agents, specifically purine nucleosides
- If needed, BRAF inhibitors can become the treatment of choice
- Excellent prognosis
What are the 3 categories of myeloid neoplasms?
- Acute myeloid leukemia (early stage maturation)
- Myelodysplastic syndrome (terminal stage maturation)
- Myeloproliferative neoplasms (normal maturation- increased or dysregular growth)
______ involves synthesis of proteins for azurophilic granules (lysosomal granulates that are similar in all three times of immature granulocytes) and other specific granules for the cytoplasm (after maturation)
Granulopoeisis
What are the stages of granulocyte maturation? (6)
- Myeloblast (most immature)
- Promyelocyte (contain basophilic cytoplasm and lysosomal enzymes)
- Myelocyte (specific lineage granules appear)
- Metamyelocyte (increasing number of granules in the cytoplasm)
- Band cell elongation
- Segmented granulocyte (complete maturation)
Myeloproliferative disorders are characterized by the presence of mutated cells with activated ______ ______ or other lesions in the ______ ______ that leads to growth factor independence.
Tyrosine kinase; signaling pathway
What is CML?
Chronic Myeloid Leukemia