WBC Disorders 4

Question 1

age of patients typically presenting with AML

Answer 1

adults, peaks at age 60

Question 2

bone pain is more common in ALL or AML?

Answer 2

ALL because it occurs in kids and the bones have tendency to expand and have a thin cortex

Question 3

organ involvement in more common in ALL or AML?

Answer 3

ALL; AML primarily occurs in the bone marrow so very rarely shows up as a mass elsewhere

Question 4

early precursors of _______ can have tissue infiltrates with monocytic infiltration

Answer 4

AML

Question 5

what are three events that account for the pathogenesis of AML?

Answer 5

• 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

Question 6

promyelocytic leukemia is associated with what translocation?
What is a common presentation of this disease?

Answer 6

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

Question 7

What are the cytogenetics associated with AML?

Answer 7

• chromosomal translocations: t(15,17), t(8,21), t(16,16)

- deletion/monosomy of chromosome 5 and 7

Question 8

what can be used to treat AML with t(15,17)?

Answer 8

ATRA (all trans retinoid acid) because it induces differentiation of neutrophils
+ chemotherapy

this is promyelocytic leukemia (AML) that usually presents with DIC

Question 9

discuss the effects of the t(15,17) translocation in promyelocytic leukemia

Answer 9

• produces a chimeric protein RAR α - PML which BLOCKS differentiation beyond promyelocytes

Question 10

myelodysplastic syndromes are due to defects in ______

Answer 10

clonal maturational defects in stem cells → ineffective hematopoiesis (abnormal differentiation) → cytopenias

Question 11

patient is found to have deletion/monosomy of chromosome 5 and 7; what condition is he at risk for developing?

Answer 11

AML, MDS

Question 12

what condition can present as refractory anemia (persistent unexplained macrocytic anemia) +/- neutropenia, thrombocytopenia, etc

Answer 12

myelodysplastic syndrome (MDS)

Question 13

patient has a RAR α chimeric protein. presents with DIC. What do you give for treatment?

Answer 13

All trans retinoid acid + chemotherapy

Question 14

what are the 4 chronic myelooproliferatwive neoplasms

Answer 14

1. CML
2. Polycythemia vera
3. Essential Thrombocytosis
4. Primary Myelofibrosis

Question 15

what is the common pathogenic feature of chronic myeloproliferative neoplasms?

Answer 15

• mutated tyrosine kinases circumvent normal growth controls resulting in growth factor independent proliferation and survival of marrow precursors
  NO IMPAIRMENT OF DIFFERENTIATION

Question 16

what is the translocation associated with CML?

Answer 16

t(9,22) leading to the BCR-ABL fusion gene → constitutive ABL kinase activation

Question 17

a person with a t(9,22) translocation develops ______. discuss the pathogenesis

Answer 17

CML; this translocation causes constitutive ABL kinase activation

Question 18

CML is a defect in ___________

Answer 18

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

Question 19

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

Answer 19

most likely CML → t(9,22)

Question 20

chronic myeloproliferative disorders are characterized by issues in _________ cells

Answer 20

pluripotent stem cells

Question 21

what is the appearance of BM in someone with CML?

Answer 21

nearly 100% cellular

Question 22

what drug is used to induce remission in patients with CML

Answer 22

imatinib/gleevec; tyrosine kinase inhibitor (inhibits the BCR-ABL kinase)
IFN α and hydroxyurea can also be used

Question 23

what are the three phases of CML

Answer 23

1. stable phase
2. accelerated phase: increasing blasts, bone marrow fibrosis, thombocytopenia, etc
3. blast crisis: CML can go to AML (75%) or to ALL (25%)

Question 24

what occurs in the accelerated phase of ____

Answer 24

CML;
1/2 of those in the stable phase will go to accelerated phase in which there is ↑ blasts, bone marrow fibrosis, and thrombocytopenia

Question 25

what occurs in the blast crisis of CML?

Answer 25

CML can transferm into AML or ALL

Question 26

imatinib/gleevec is used to treat ______

Answer 26

CML because it inhibits the BCR-Abl tyrosine kinase

Question 27

CML most commonly progresses into _____ and less often to _____

Answer 27

AML 75%

ALL 35%

Question 28

describe the prognosis of treating CML with gleevec/imatinib

Answer 28

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