Chronic Myelogenous Leukemia

Question 1

What happens in myeloproliferative disorders?

Answer 1

Increased production of one or more totes of blood cells

Question 2

Myeloproliferative disorders can transform to _______________ (acute myeloid leukaemia/chronic lymphocytic leukaemia)

Answer 2

Acute myeloid leukaemia

Question 3

Chronic myelogenous leukaemia (a type of MPD) can transform into _______________

Answer 3

Acute lymphocytic leukaemia

Question 4

The common pathogenic feature of MPDs is the presence of mutated, activated ___________ that lead to growth factor independence.

Answer 4

Tyrosine kinases

Question 5

MPDs do not impair differentiation so the most common effect is an __________ (increase/decrease) in the production of one or more mature blood elements

Answer 5

Increase

Question 6

What are the main features of MPDs?

Answer 6

1. Increased proliferation in bone marrow
2. Homing of neoplastic stem cells to secondary hematopoietic organs —> Extramedullary hematopoiesis
3. Transformation to a spent phase (marrow fibrosis and peripheral blood cytopenias)
4. Variable transformation to acute leukaemia

Question 7

Systemic mastocytosis is a MPD that is associated with mutations in the _____ tyrosine kinase

Answer 7

KIT

Question 8

Chronic myelogenous leukaemia is characterized by presence of chimeric __________ gene

Answer 8

BCR-ABL gene

Question 9

BCL gene is on chromosome no. _____

Answer 9

22

Question 10

ABL gene is on chromosome no. ____

Answer 10

9

Question 11

In more than 90% of the cases, BCR-ABL is created by a _______________

Answer 11

Reciprocal translocation (9;22) (q34;q11)

Question 12

Reciprocal translocation (9;22) (q34;q11) is also called the _______________ chromosome.

Answer 12

Philadelphia

Question 13

The cell of origin is a ____________(pluripotent/multipotent) hematopoietic stem cell in CML.

Answer 13

Pluripotent

Question 14

The _____ moiety of BCR-ABL contains a dimerization domain that self associates, leading to the activation of the other tyrosine kinase moiety in CML.

Answer 14

ABL

Question 15

The marrow is markedly __________ (hypocellular/hypercellular) in CML.

Answer 15

Hypercellular

Because of massively increased numbers of maturing granulocytic precursors

Question 16

___________ (increased/decreased) proportion of eosinophils and basophils is found in CML.

Answer 16

Increased

Question 17

Megakaryocytes are ___________ (increased/decreased) and usually include
small, dysplastic forms and so are platelets in CML

Answer 17

Increased

Question 18

Erythroid progenitors are present in

normal or mildly __________ (increased/decreased) numbers in CML.

Answer 18

decreased

Question 19

A characteristic finding is the presence of scattered macrophages with abundant wrinkled, green-blue cytoplasm so-called _______________ in CML.

Answer 19

Sea green histiocytes

Question 20

_________ (Increased/decreased) deposition of reticulin is typical in CML

Answer 20

Increased

Question 21

Overt marrow fibrosis occurs ______ (early/late) in the course of CML.

Answer 21

late

Question 22

The blood reveals a leukocytosis, often exceeding __________ (50,000/100,000) cells/mm3 which consists predominantly of neutrophils, band forms, metamyelocytes, myelocytes, eosinophils, and basophils in CML.

Answer 22

100,000 cells/mm3

Question 23

Blasts usually make up less than ___% of the circulating cells in CML

Answer 23

10

Question 24

The spleen is often greatly enlarged as a result of extensive __________ (hemolysis/extramedullary hematopoiesis) and often contains infarcts of varying age in CML

Answer 24

extramedullary hematopoiesis

Question 25

_______________ can also produce mild hepatomegaly and lymphadenopathy

Answer 25

Extramedullary hematopoiesis

Question 26

CML is primarily a disease of _________ (adults/children)

Answer 26

adults

Question 27

The peak incidence is in the ______ (5th-6th/3th-4th) decades of life in CML

Answer 27

5th-6th

Question 28

What are the symptoms of CML?

Answer 28

``` Mild-to-moderate anemia Hypermetabolism Fatigability Weakness Weight loss Anorexia. Dragging sensation in the abdomen Acute onset of left upper quadrant pain ```

Question 29

Why is hypermetabolism going on in patient with CML

Answer 29

Due to increased cell turnover leading to fatigabililty

Question 30

What can be the reason of dragging sensation of abdomen in CML?

Answer 30

enlarged spleen

Question 31

What is the reason of acute onset of left upper quadrant pain in CML?

Answer 31

Splenic infarcts

Question 32

The natural history is one of slow progression; even | without treatment, the median survival is about _________ (1 year/3 years)

Answer 32

3 years

Question 33

After a variable period averaging 3 years, about 50% of | patients enter an ________ (accelerated/spent) phase of CML

Answer 33

accelerated

Question 34

What happens in accelerated phase of CML?

Answer 34

Increasing anemia and thrombocytopenia sometimes accompanied with a rise in basophils.

Question 35

What is the duration of accelerated phase of CML?

Answer 35

After 6-12 months, the accelerated phase terminates in acute leukemia (blast crisis)

Question 36

Give examples of additional clonal cytogenetic abnormalities that often appear in accelerated phase of CML.

Answer 36

Trisomy 8 Isochromosome 17q Duplication of the Ph chromosome

Question 37

In the other ___% of patients, blast crises occur | abruptly without an accelerated phase in CML

Answer 37

50%

Question 38

In 70% of crises, the blasts are of _________ (myeloid/lymphoid) origin in CML.

Answer 38

myeloid

Question 39

The remaining 30% blasts are of _________ (pre–B cell/pre–T cell) origin in lymphoid blast crises of CML

Answer 39

pre–B cell origin

Question 40

What is the evidence that CML originates from pluripotent stem cell?

Answer 40

Both type of blast crises occurs (myeloid and lymphoid)

Question 41

Acute leukemia stems from two complementary mutations. What are these mutations?

Answer 41

Mutation in transcriptional factor and tyrosine kinase

Question 42

Blast crises occurs due to the mutation of ____________ in CML

Answer 42

transcription factor

Question 43

In lymphoid blast crisis, 85% of cases are associated with mutations that interfere with the activity of ________.

Answer 43

Ikaros

Question 44

What is Ikaros?

Answer 44

A transcription factor that regulates the differentiation of hematopoietic progenitors

Question 45

Ikaros mutations are also seen in BCR-ABL positive _________

Answer 45

B-ALL

Question 46

Treatment with _________ inhibitors results in sustained hematologic remissions in greater than 90% of patients.

Answer 46

BCR-ABL inhibitors

Question 47

For relatively young patients, ______________ performed in the stable phase is curative in about 75% of cases.

Answer 47

Hematopoietic stem cell transplantation

Question 48

The treatment is less effective in __________ (stable/accelerated) phase

Answer 48

accelerated

Question 49

What exactly is the function of BCR-ABL inhibitors?

Answer 49

1. They decrease the number of BCR-ABL-positive cells in the marrow 2. They decrease the rate at which these cells acquire mutations 3. They control blood counts and decrease the risk of transformation to the accelerated phase and blast crisis.