WBC Disorders 4 Flashcards
age of patients typically presenting with AML
adults, peaks at age 60
bone pain is more common in ALL or AML?
ALL because it occurs in kids and the bones have tendency to expand and have a thin cortex
organ involvement in more common in ALL or AML?
ALL; AML primarily occurs in the bone marrow so very rarely shows up as a mass elsewhere
early precursors of _______ can have tissue infiltrates with monocytic infiltration
AML
what are three events that account for the pathogenesis of AML?
- block in terminal differentiation due to translocations and chimeric genes that form abnormal fusion proteins
- increased cellular proliferation due to mutated tyrosine kinases
- suppression of the normal hematopoietic progenitors due to the accumulation of neoplastic precursors in the BM
promyelocytic leukemia is associated with what translocation?
What is a common presentation of this disease?
t(15,17); presents as DIC because the Auer rods are can cause a severe reaction with the cells are broken and release these Auer rods
What are the cytogenetics associated with AML?
- chromosomal translocations: t(15,17), t(8,21), t(16,16)
- deletion/monosomy of chromosome 5 and 7
what can be used to treat AML with t(15,17)?
ATRA (all trans retinoid acid) because it induces differentiation of neutrophils
+ chemotherapy
this is promyelocytic leukemia (AML) that usually presents with DIC
discuss the effects of the t(15,17) translocation in promyelocytic leukemia
- produces a chimeric protein RAR α - PML which BLOCKS differentiation beyond promyelocytes
myelodysplastic syndromes are due to defects in ______
clonal maturational defects in stem cells → ineffective hematopoiesis (abnormal differentiation) → cytopenias
patient is found to have deletion/monosomy of chromosome 5 and 7; what condition is he at risk for developing?
AML, MDS
what condition can present as refractory anemia (persistent unexplained macrocytic anemia) +/- neutropenia, thrombocytopenia, etc
myelodysplastic syndrome (MDS)
patient has a RAR α chimeric protein. presents with DIC. What do you give for treatment?
All trans retinoid acid + chemotherapy
what are the 4 chronic myelooproliferatwive neoplasms
- CML
- Polycythemia vera
- Essential Thrombocytosis
- Primary Myelofibrosis
what is the common pathogenic feature of chronic myeloproliferative neoplasms?
- mutated tyrosine kinases circumvent normal growth controls resulting in growth factor independent proliferation and survival of marrow precursors
NO IMPAIRMENT OF DIFFERENTIATION
what is the translocation associated with CML?
t(9,22) leading to the BCR-ABL fusion gene → constitutive ABL kinase activation
a person with a t(9,22) translocation develops ______. discuss the pathogenesis
CML; this translocation causes constitutive ABL kinase activation
CML is a defect in ___________
defect in pluripotent stem cell for myeloid and lymphoid lineage BUT the morphologic expression is mainly granulocytic (uncontrolled proliferation with full differentiation) so will see ↑ neutrophils, eosinophils, etc
on peripheral blood smear, you see striking left shifted leukocytosis with mainly neutrophils and metamyelocytes, myelocytes, eosinophils and basophils. What is the translocation associated with this disease
most likely CML → t(9,22)
chronic myeloproliferative disorders are characterized by issues in _________ cells
pluripotent stem cells
what is the appearance of BM in someone with CML?
nearly 100% cellular
what drug is used to induce remission in patients with CML
imatinib/gleevec; tyrosine kinase inhibitor (inhibits the BCR-ABL kinase)
IFN α and hydroxyurea can also be used
what are the three phases of CML
- stable phase
- accelerated phase: increasing blasts, bone marrow fibrosis, thombocytopenia, etc
- blast crisis: CML can go to AML (75%) or to ALL (25%)
what occurs in the accelerated phase of ____
CML;
1/2 of those in the stable phase will go to accelerated phase in which there is ↑ blasts, bone marrow fibrosis, and thrombocytopenia
what occurs in the blast crisis of CML?
CML can transferm into AML or ALL
imatinib/gleevec is used to treat ______
CML because it inhibits the BCR-Abl tyrosine kinase
CML most commonly progresses into _____ and less often to _____
AML 75%
ALL 35%
describe the prognosis of treating CML with gleevec/imatinib
mainly morphological remission
imatinib inhibits the BCR-ABL kinase and SLOWS DOWN the disease but does not destroy the abnormal clone
DOES NOT PREVENT THE BLAST CRISIS
