Acute leukemia, myeloproliferative, and myelodysplastic syndromes

Question 1

In acute leukemia, cells are rapidly proliferating but _______

Answer 1

undifferentiated/ immature

Question 2

Myelodysplastic syndromes are characterized by _______ in which the bone marrow may be hypercellular but peripheral counts are low

Answer 2

ineffective hematopoiesis

Question 3

In myelodysplastic syndromes, cell differentiation is (normal/ abnormal)

Answer 3

abnormal- neutrophils, red cells, platelets, and precursors are morphologically and functionally aberrant

Question 4

In myelodysplastic syndromes, the cells are (mature/immature)

Answer 4

mature

Question 5

Acute ____ leukemia is more common with aging and in men

Answer 5

myelogenous

Question 6

Acute _____ leukemia is most common in childhood

Answer 6

lymphoblastic

Question 7

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

Answer 7

(8;21) translocation

Question 8

Describe the normal role of CBF and how its function is aberrant in (8;21) AML

Answer 8

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

Question 9

What is the prognosis for CBF- related AML?

Answer 9

Generally good, treatment responsive

Question 10

What is the prognosis for AML or ALL with the 9;22 translocation?

Answer 10

Philadelphia chromosome- poor prognosis

Question 11

Describe the cause and prognosis of APML

Answer 11

15;17 translocation involving the retinoic acid receptor, associated with severe DIC but responds to treatment with ATRA

Question 12

List the main two problems associated with acute leukemia

Answer 12

bone marrow failure

organ dysfunction from proliferating leukemia cells

Question 13

What is leukostasis?

Answer 13

aggregates of leukemic cells cause vascular congestion, occlusion of small vessels, and ischemia that affects multiple organs

Question 14

How can AML be distinguished from ALL on the peripheral blood smear?

Answer 14

Auer rods in AML

Question 15

What CD molecules would be on the surface of a cell in a patient with AML?

Answer 15

proteins consistent with myeloid lineage- CD13 and CD33

Question 16

What CD molecules can be used to distinguish B cell vs T cell ALL?

Answer 16

B cell ALL: CD19, CD22, CD10

T cell ALL: CD7, CD3, CD2

Question 17

What is the significance of expression of TdT in acute leukemia?

Answer 17

Favors lymphoid lineage

TdT is an enzyme necessary for Ig and T cell receptor rearrangement

Question 18

In the setting of acute leukemia, it is standard practice to immediately treat febrile and neutropenic patients with ______

Answer 18

broad spectrum antibiotics

can back off after getting results of cultures

Question 19

The most effective drugs are cycle-specific agents that attack cells during ______

Answer 19

S phase- DNA synthesis

Question 20

True or false: with advances in treatment, AML now has a five year survival rate of nearly 90%

Answer 20

False: 45% for patients younger than 45 and 2% for patients older than 75- still highly lethal

Better survival in ALL

Question 21

________ disorders are characterized by the abnormal proliferation of myeloid stem cells that retain the ability to differentiate and whose progeny function normally

Answer 21

Myeloproliferative

Question 22

List four myeloproliferative diseases

Answer 22

CML
polycythemia vera
essential thrombocytosis
primary myelofibrosis

Question 23

CML is defined by the presence of the _____ chromosome

Answer 23

Philadelphia

Question 24

The Philadelphia chromosome is formed by the 9;22 translocation which causes the formation of the _______ fusion gene

Answer 24

brc-abl

Question 25

The Philadelphia chromosome is also found in some cases of ___ and ____ and portends a poor prognosis in those diseases

Answer 25

AML and ALL

Question 26

What is seen in the peripheral blood in CML?

Answer 26

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

Question 27

List some presenting symptoms of CML

Answer 27

Fever, night sweats, fatigue, anorexia and abdominal pain (enlarged spleen)

Question 28

______ of CML is accompanied by a progressive block in differentiation in which mature WBCs in the marrow are replaced by blasts

Answer 28

Transformation

Question 29

What drug is used to inhibit the tyrosine kinase formed by the bcr-abl fusion gene?

Answer 29

Imatinib

Question 30

List some common presenting symptoms of polycythemia vera

Answer 30

``` Headache, fatigue, dizziness, night sweats, visual disturbance, weight loss Aqugenic pruritis (mast cells) ```

Question 31

List some physical exam and lab findings in polycythemia vera

Answer 31

``` splenomegaly plethora hepatomegaly systolic HTN portal vein thrombosis hypercellular marrow ```

Question 32

Polycythemia vera is associated with a mutation in _____

Answer 32

JAK2 | - EPO independent hematopoiesis

Question 33

List therapies used in polycythemia vera

Answer 33

Phlebotomy (induces Fe deficiency) aspirin hydroxyurea ruxolitnib (inhibits JAK2)

Question 34

Many patients with essential thrombocytosis have JAK2 mutations. Other common mutations include:

Answer 34

MPL, thrombopoietin receptor, or calreticulin (CALR) gene

Question 35

List therapies for essential thrombocytosis

Answer 35

hydroxyurea aspirin to prevent thrombosis possibly no treatment

Question 36

In primary myelofibrosis, fibrous tissue infiltrates and replaces normal marrow in response to:

Answer 36

growth signals released by neoplastic hematopoietic stem cells and their progeny

Question 37

What cell morphology is seen with primary myelofibrosis

Answer 37

tear drop cells / dacryocytes

Question 38

What drug can be used in primary myelofibrosis, and how successful is it?

Answer 38

JAK2 inhibitor ruxolitnib | Still very poor prognosis

Question 39

Describe myelodysplastic syndrome

Answer 39

heterogeneous group of clonal hematopoietic stem cell disorders characterized by inability to produce adequate numbers of white cells, red cells, and/or platelets. abnormal differentiation in the progeny of the affected stem cells, causing many of them to undergo apoptosis before reaching maturity--> ineffective hematopoiesis

Question 40

MDS is characterized by a _____ marrow but ____ production of mature blood cells

Answer 40

Hypercellular marrow | decreased production

Question 41

___________ is a potential long term complication of treatment of other cancers

Answer 41

MDS

Question 42

Describe cell morphologies seen in myelodysplastic syndromes

Answer 42

usually anemic/ pancytopenic neutrophils are hypolobated/ hypogranular megaloblastic changes in RBCs Ringed sideroblasts

Question 43

MDS can develop over time into a form of _____

Answer 43

AML