Acute Leukemias Flashcards
How frequent are chromosomal abnormalities in AML and ALL, and what general consequences do they have?
Chromosomal abnormalities are present in 95% of AML and 90% of ALL cases. They affect oncogenes, tumor suppressor genes, and apoptosis pathway genes, leading to a situation where both maturation/differentiation is blocked and cells are not dependent on external factors for growth.
At what stage of the cell line do AML mutations occur?
Genetic perturbations occur at the level of the pluripotent stem cell or one of the committed progenitors. Thus, AML cells may be from any of the myeloid lineages. This also leads to the existence of “leukemic stem cells” which have unlimited potential for self-renewal and proliferation.
At what stage of the cell line to ALL mutations occur?
Genetic perturbations in ALL occur at the level of the lymphoid stem cell. Clonal progeny of the affected cell commit to B or T-cell lineage, but maturation is blocked at one of the early stages.
What are the risk factors associated with acute leukemias?
1) Previous chemotherapy, esp. involving DNA alkylating agents or topoisomerase-II inhibitors. 2) Tobacco smoke. 3) Ionizing radiation. 4) Benzene exposure. 5) Genetic disorders including Down Syndrome, Bloom syndrome, Fanconi anemia, and ataxia-telangiectasia. Most patients with acute leukemias will NOT have any predisposing risk factors.
What are the symptoms of acute leukemia?
Fatigue; Malaise; Dyspnea; Easy bruising; Weight loss; Sometimes bone or abdominal pain; rarely neurological symptoms.
What are the signs of acute leukemia?
Anemia and pallor; Thrombocytopenia (hemorrhage, petechiae, ecchymoses); Fever and infection (pneumonia, sepsis); Adenopathy, hepatosplenomegaly, mediastinal mass; rarely Gum or skin infiltration, renal enlargement and insufficiency, and cranial neuropathy.
What is leukopheresis and when is it used?
Leukopheresis is the mechanical removal of white blood cells from the peripheral blood. It is used when there is a severe excess of white blood cells that are causing hyperviscosity or thrombotic problems.
How is ALL diagnosed?
ALL does not have a set percentage of lymphocytes required (usually extremely high anyway). Lymphoblasts tend to be smaller than myeloblasts, but actual designation and assignment of T or B lineage depends on immunophenotyping. Lymphoblasts express TdT (lymphoblast immaturity), and CD34 (immaturity marker) which is also expressed by myeloblasts
What is the proportion of ALL cases that are B cell derived and what markers do they display?
80-85% of ALL cases are B-ALL. They express B-lineage antigens CD19, CD22, and/or CD79a. They usually do NOT express markers of mature B-cells including CD20 or surface Ig.
What are the cytogenic markers of B-ALL?
t(9;22) BCR-ABL1 Produces smaller BCR-ABL product (190kd) and has the worst prognosis of all ALL subtypes. Translocations of 11q23 MLL frequently seen in B-ALL of neonates and infants (<1 yo ALL patients. t(12:21) ETV6-RUNX1 Very favorable prognosis
What is the frequency and hallmarks of T-ALL?
T-ALL is the minority of ALL cases (20-25%). More common in adolescents and young adults than children and favors males over females. Also more often has an LBL mass, usually a mediastinal mass.
What markers does T-ALL often express?
T-ALL expresses the T-lineage antigens CD2, CD3, and/or CD7. May express both CD4 and CD8, either one, or neither. Often express immaturity markers CD99 and CD1a.
How is AML diagnosed and what antigenic (CD) markers are present? For Monocytes? For megakaryoblasts?
> 20% myeloblasts in the marrow or peripheral blood. Presence of Auer Rods. Presence of CD34, CD117, or Myeloperoxidase. Monocytic differentiation is marked by CD64 & CD14. Megakaryoblastic differentiation is marked by CD41 and CD61.
What are some important cytogenic findings related to AML?
t(15:17) PML-RARA (APL) Treatable with retinoid acid (vitamin A), good prognosis, associated with DIC. t(1:22) Infants with Down Syndrome, megakaryoblastic diff and good prognosis. Abnormal 11q23 MLL Gene may be fused with multiple different partners (hence only one gene listed, no translocation) Monocytic differentiation, poor prognosis
What is t-AML and what causes it?
Therapy related AML arises secondary to DNA damage from prior chemotherapy, usually due to DNA alkylating agents or topoisomerase inhibitors. Alkylating agents: 2-8 years after treatment, loss of chromosome 5 or 7. Topoisomerase Inh: 1-2 years after treatment, rearrangement of MLL 11q23. All forms of t-AML have very poor prognosis.
