Flashcards in Acute leukemia, myeloproliferative, and myelodysplastic syndromes Deck (43):
In acute leukemia, cells are rapidly proliferating but _______
Myelodysplastic syndromes are characterized by _______ in which the bone marrow may be hypercellular but peripheral counts are low
In myelodysplastic syndromes, cell differentiation is (normal/ abnormal)
abnormal- neutrophils, red cells, platelets, and precursors are morphologically and functionally aberrant
In myelodysplastic syndromes, the cells are (mature/immature)
Acute ____ leukemia is more common with aging and in men
Acute _____ leukemia is most common in childhood
The form of AML with a _______ translocation is also called core binding factor leukemia because the translocation affects the CBF complex that controls myeloid differentiation
Describe the normal role of CBF and how its function is aberrant in (8;21) AML
CBF will bind and attract a collection of transcriptional activators that are required for
transcription of genes necessary for neutrophil maturation
In the 8;21 translocation, CBF-ETO chimeric protein functions as an attractor of transcriptional repressor proteins, and effectively blocks the next step in myeloid differentiation- neutrophils do not differentiate but can divide and proliferate
What is the prognosis for CBF- related AML?
Generally good, treatment responsive
What is the prognosis for AML or ALL with the 9;22 translocation?
Philadelphia chromosome- poor prognosis
Describe the cause and prognosis of APML
15;17 translocation involving the retinoic acid receptor, associated with severe DIC but responds to treatment with ATRA
List the main two problems associated with acute leukemia
bone marrow failure
organ dysfunction from proliferating leukemia cells
What is leukostasis?
aggregates of leukemic cells cause vascular congestion, occlusion of small vessels, and ischemia that affects multiple organs
How can AML be distinguished from ALL on the peripheral blood smear?
Auer rods in AML
What CD molecules would be on the surface of a cell in a patient with AML?
proteins consistent with myeloid lineage- CD13 and CD33
What CD molecules can be used to distinguish B cell vs T cell ALL?
B cell ALL: CD19, CD22, CD10
T cell ALL: CD7, CD3, CD2
What is the significance of expression of TdT in acute leukemia?
Favors lymphoid lineage
TdT is an enzyme necessary for Ig and T cell receptor rearrangement
In the setting of acute leukemia, it is standard practice to immediately treat febrile and neutropenic patients with ______
broad spectrum antibiotics
can back off after getting results of cultures
The most effective drugs are cycle-specific agents that attack cells during ______
S phase- DNA synthesis
True or false: with advances in treatment, AML now has a five year survival rate of nearly 90%
False: 45% for patients younger than 45 and 2% for patients older than 75- still highly lethal
Better survival in ALL
________ disorders are characterized by the abnormal proliferation of myeloid stem cells that retain the ability to differentiate and whose progeny function normally
List four myeloproliferative diseases
CML is defined by the presence of the _____ chromosome
The Philadelphia chromosome is formed by the 9;22 translocation which causes the formation of the _______ fusion gene
The Philadelphia chromosome is also found in some cases of ___ and ____ and portends a poor prognosis in those diseases
AML and ALL
What is seen in the peripheral blood in CML?
Granulocytic precursors at all levels of development with a differential similar to normal bone marrow
Basophils and eosinophils
WBC count very high, platelets usually elevated, hematocrit is normal or low
List some presenting symptoms of CML
Fever, night sweats, fatigue, anorexia and abdominal pain (enlarged spleen)
______ of CML is accompanied by a progressive block in differentiation in which mature WBCs in the marrow are replaced by blasts
What drug is used to inhibit the tyrosine kinase formed by the bcr-abl fusion gene?
List some common presenting symptoms of polycythemia vera
Headache, fatigue, dizziness, night sweats, visual disturbance, weight loss
Aqugenic pruritis (mast cells)
List some physical exam and lab findings in polycythemia vera
portal vein thrombosis
Polycythemia vera is associated with a mutation in _____
- EPO independent hematopoiesis
List therapies used in polycythemia vera
Phlebotomy (induces Fe deficiency)
ruxolitnib (inhibits JAK2)
Many patients with essential thrombocytosis have JAK2 mutations. Other common mutations include:
MPL, thrombopoietin receptor, or calreticulin (CALR) gene
List therapies for essential thrombocytosis
aspirin to prevent thrombosis
possibly no treatment
In primary myelofibrosis, fibrous tissue infiltrates and replaces normal marrow in response to:
growth signals released by neoplastic hematopoietic stem cells and their progeny
What cell morphology is seen with primary myelofibrosis
tear drop cells / dacryocytes
What drug can be used in primary myelofibrosis, and how successful is it?
JAK2 inhibitor ruxolitnib
Still very poor prognosis
Describe myelodysplastic syndrome
heterogeneous group of clonal hematopoietic stem cell disorders characterized by inability to produce adequate numbers of white cells, red
cells, and/or platelets.
in the progeny of the affected stem cells, causing many of them to undergo apoptosis before reaching maturity--> ineffective hematopoiesis
MDS is characterized by a _____ marrow but ____ production of mature blood cells
___________ is a potential long term complication of treatment of other cancers
Describe cell morphologies seen in myelodysplastic syndromes
usually anemic/ pancytopenic
neutrophils are hypolobated/ hypogranular
megaloblastic changes in RBCs