Acute Leukemias Flashcards
(41 cards)
What are general features of acute leukemias?
Unregulated proliferation of blast cells in the bone marrow (>20%) leading to inhibition of normal hematopoiesis
What do leukemias typically look like in the peripheral blood?
Blasts enter the bloodstream, resulting in a high WBC count. They are large, immature clonal cells with punched out nucleoli.
How does inhibition of normal hematopoiesis explain the classic signs of acute leukemias?
Anemia -> fatigue, pallor
Thrombocytopenia -> bleeding (ecchymosis, epistaxis, menorrhagia, petechiae)
Neutropenia -> infections
Fever / bone pain from crowding out of bone marrow by blast cells
What is the most common acute leukemia in adults and what are the risk factors?
Acute myeloid leukemia (AML)
- Down syndrome
- Radiation and alkylating chemotherapy
- Myeloproliferative disorders
What is a myeloid sarcoma and give one example of a manifestation of it?
Solid tumor of leukemic myeloid cells occurring outside the bone marrow
- > sometimes a presentation of AML
- > common in skin, heart, testes, and brain
- > Leukemia cutis - when myeloid blast cells infiltrate the tissues
What tissue infiltration is characteristic of acute monocytic leukemia?
Gingival hypertrophy -> monoblasts have a tropism for the gums
Keep in mind this is a type of AML
What is APL, what mutation is associated with it, and what is the mechanism?
Acute Promyelocytic Leukemia
-> associated with t(15;17) translocation, where RAR receptor on chromosome 17 is disrupted by PML gene, blocking promyelocyte differentiation
What leukemias are associated with Down syndrome and at what ages?
Before age 5: Acute megakaryoblastic anemia (type of AML)
After age 5: Acute lymphoblastic leukemia (ALL)
How do the blasts look in AML on peripheral smear?
immature cells with large nuclei, prominent (punched out) nucleoli, fine granular chromatin, pale blue cytoplasm, and granules
with a pathognomonic finding
What finding is pathognomonic of AML? What are they?
Auer Rods in the cytoplasm of blast cells
They are crystal aggregates of myeloperoxidase (MPO)
For this reason these cells are MPO+
What type of AML sees the most Auer rods?
Acute Promyelocytic Leukemia -> differentiating into neutrophils so they will have the most MPO
How does leukemic vs normal bone marrow look different in general?
In normal bone marrow, cell populations are very diverse
In leukemia - there will be clonal proliferations of blast cells crowding out diversity
Other than myeloperoxidase staining, give two other stains used to differentiate AML from ALL.
- Sudan Black stain - only stains myeloblasts but not lymphoblasts
- Non-specific esterase - identifies cells of monocyte origin
What are the myeloid markers by flow cytometry?
CD13, CD33
What are the monocyte markers for flow cytometry?
CD11 (integrin receptors for ICAM binding)
CD14 (TLR4)
What is the immature hematopoietic stem cell marker? If it’s a lymphoid cell specifically?
CD34
Specifically lymphoid cells:
TdT = special DNA prolymerase
-> only seen in lymphoBLASTS, not mature lymphocytes
What are the flow cytometry markers for B-cell ALL?
CD10
CD19
CD20
CD22
What are the flow cytometry markers for T cell ALL?
CD2, CD3, CD7 (numbers 2-8, will NOT express CD10)
Are cytogenetic changes associated with AML?
Yes, greater than 50% of patients have abnormal karyotypes of some kind on analysis of metaphase-dividing cells
-> i.e. Philadelphia chromosome, preceded by CML
When in the cell cycle does FISH identify abnormalities? What abnormalities can you find?
In the interphase / nondividing cells
Can see microdeletions, translocations (i.e. philadelphia chromosomes), and duplications
What genetic analysis is done on leukemic cells and why? Which AML has the worst prognosis? Best?
Whole genome molecular marker analysis
Worst: FLT-3+ (FMS-related tyrosine kinase)
Best: NPM1+, CEBPA+
NPM: Nucleophosphomin
What are the three AML’s which do NOT require >20% blasts in bone marrow to diagnose them as AML (this is unique)? What is wrong in the first two of them?
First two are related to dysfunction in core binding factors (CBF) which are essential for normal hematopoesis
- t(8;21) - RUNX1 - remember one less than 9;22
- inversion (16)
- t(15;17) - RAR dysfunction promyelocytic leukemia
How do you recognize APL and why is it important to recognize it early? What do RBCs look like in it?
Cells are distinctive because of many cytoplasmic granules and stacks of Auer rods (MPO+)
Recognize early because when cells are lysed, MPO activates coagulation cascade, causing a procoagulant state
DIC is a common presentation in these patients
RBCs - schistocytes due to microangiopathic cleavage
What is the treatment for APL?
All-trans retinoic acid (Atra)
-> induces differentiation of promyelocytes
