Flashcards in Acute Leukemias Deck (33):
What is the difference between an acute neoplasm and a chronic neoplasm?
Acute - presence of immature cells (Blasts)
Chronic- presence of differentiated (mature) cells
Both may be of either Lymphoid or Myeloid origin
What is leukemia?
Malignant neoplasm characterized by the replacement of the bone marrow by neoplastic cells
What is a lymphoma?
Proliferations of hematopoietic neoplasms arising as discrete tissue masses
In general, what are some clinical features of acute leukemias?
Abrupt stormy onset
Suppression of normal hematopoiesis
Anemia - fatigue
Neutropenia - fever
Thrombocytopenia - bleeding
What are some symptoms that are more likely to occur in ALL than AML?
ALL more likely to have generalized lymphadenopathy, splenomegaly, hepatomegaly, CNS involvement
What acute leukemia are kids more likely to acquire?
What are the neoplastic cells in ALL?
Lymphoblasts (B or T lymphoblasts)
85% of ALLs are pre-B cell neoplasms
What are the special clinical features of T-ALL?
Commonly presents in adolescent males with thymic involvement
Presents as a mediastinal mass
How is the diagnosis of ALL made?
Microscopic analysis -
See lymphoblasts with scant basophilic cytoplasm and fine nuclear chromatin
Flow cytometry for T and B cell markers
What is the specific stain used to diagnose ALL?
Terminal deoxynucleotidyl transferase
Positive in over 95% of ALLs
What are some common chromosomal abnormalities with ALL?
Hyperdiploidy (over 50 chromosomes)
t(9;22) - BCR-ABL; Philadelphia chromosome
t(4;11) (MLL gene)
What is the general prognosis for ALL?
Complete remission rates of 90% or better in children
Cure in up to 2/3 patients
What are some favorable prognostic indicators of ALL?
TEL-AML t(12;21) mutation
What are some unfavorable prognostic indicators of ALL?
Diagnosis before 2
Adolescent or adult presentation
Presence of t(9;22) (Philadelphia chromosome)
Which leukemia are adults more likely to acquire?
AML is a highly heterogeneous disease. What cell types may AML involve?
What are some general causes of AML (the four main categories of WHO classification)?
1. AML with recurrent genetic abnormalities
2. AML arising from myelodysplastic syndrome
3. Therapy related
4. Not otherwise specified
What are the two most important mutations associated with AML?
What is myelodysplastic syndrome (MDS)?
Clonal stem cell disorder with defective and ineffective hematopoiesis with increased risk of transformation to AML
Could be idiopathic or therapy related (after chemo)
Describe the pathophysiology of MDS
Hypercellular marrow with peripheral cytopenia
Cells are produced but they undergo apoptosis in the bone marrow itself, so they never make ti to the periphery
Could be cause by clonal cytogenetic abnormalities, stem cell damage, or morphologic abnormalities
What are the morphological abnormalities associated with MDS?
Separated nuclear lobes
What is the prognosis of MDS?
9-29 months for primary MDS, 4-8 months for secondary.
Subtypes of MDS with more blasts in the blood or marrow have a worse prognosis
What are the clinical findings of AML?
Abrupt stormy onset
Not much tissue involvement
Lower chance of CNS involvement
Acute Promyelocytic Leukemia (APL)
What mutation causes this disorder?
How is APL related to DIC?
Procoagulants (tissue factor) may be released by leukemic cells to induce DIC in APL patients
What is the characteristic finding of APL on microscopic analysis?
Auer rods in the cytoplasm
Describe the pathogenesis of APL
Leads to an abnormal RAR-a receptor, which blocks myeloid differentiation
What is the normal function of the RAR-alpha receptor?
Involved in activating the differentiation of myeloid cells
How could you treat APL with a t(15;17) mutation?
High doses of All-trans-retinoic acid (vitamin A derivative) will overcome the block of the RAR-alpha receptor
What two chemical stains may be used in the diagnosis of AML?
Alpha-naphthyl butyrate esterase
What markers should be looked at on flow cytometry for suspected AML?
What is an Auer rod? What does its presence tell you?
Auer rods are made of MPO which crystallizes and forms rod structures
Presence of Auer rod tells you it is a malignant myeloid cell