MPN

Question 1

are clonal hemato-
poietic disorders caused by genetic mutations in the hemato-
poietic stem cells (HSCs) that result in expansion, excessive
production, and accumulation of mature erythrocytes, granu-
locytes, and platelets

Answer 1

myeloproliferative neoplasms (MPNs)

Question 2

MPN is predominantly chronic or acute

Answer 2

chronic

Question 3

World Health Organization (WHO) has classified the
MPNs into four predominant disorders

Answer 3

1. Chronic Myeloid
   Leukemia (CML)
2. Polycythemia Vera (PV)
3. Essential (primary) Thrombocythemia
   (ET)
4. Primary myelofibrosis (PMF)

Question 4

(+) BCR-ABL1

Answer 4

Chronic Myeloid Leukemia

Question 5

(-) BCR-ABL1 and JAK 2 Mutation

Answer 5

Polycythemia Vera
Essential Thrombocytopenia
Primary Myelofibrosis

Question 6

The critical changes from the origi-
nal French-American-British (FAB) classification to the WHO
classification system for the MPNs include the following

Answer 6

(1) Ph
and/or the BCR-ABL1 fusion gene is required for a diagnosis of
CML;
(2) minimum BM blast count
threshold to differentiate
MPNs from ALs is reduced from 30% to 20%; and
(3) eosinophil disorders have been reclassified.

Question 7

Ph- and BCR-ABL1-negtive cases with myelodysplastic and myeloproliferative features are included in the WHO myelodysplastic syndrome (MDS)/MPN group

Answer 7

atypical CML (aCML)

Question 8

single genetic translocation in a
pluripotential HSC producing a clonal overproduction of the
myeloid cell line, resulting in a preponderance of immature cells
in the neutrophilic line.

Answer 8

Chronic Myeloid Leukemia

Question 9

Phases of CML

Answer 9

CML begins with a chronic clinical phase
and, if untreated, progresses to an accelerated phase in 3 to
4 years and often terminates as an AL (blast crisis phase). Progression to AL can be of the myeloid type (AML) or the lymphoid type (ALL)

Question 10

incidence of CML

Answer 10

-occurs at all ages
-predominantly seen in 46-53 years of age
-responsible for 20% of leukemia
-common in males than in females

Question 11

genetic bases of CML

Answer 11

1. the Philadelphia chromosome, is present in proliferating HSCs and their progeny in CML and must be identified to confirm the diagnosis.
2. reciprocal translocation between the long arms of chromosomes 9 and 22 produces BCR-ABL1 fusion protein

Question 12

normally ABL1 codes for

Answer 12

p125 which exhibits normal tyrosine kinase activity

Question 13

normally BCR1 codes for

Answer 13

p160 which expresses serine and threonine kinase activity, and is thought to function in the regulation of cell growth.

Question 15

are enzymes that catalyze the transfer of phosphate
groups from adenosine triphosphate (ATP), guanosine tri-
phosphate (GTP), and other phosphate donors to receiver
proteins.

Answer 15

Protein Kinases

Question 16

pathogenesis of cmp

Answer 16

the
BCR-ABL1 tyrosine kinase loses the ability to shut off kinase
activity and is said to have constitutive tyrosine kinase activity.

The BCR-ABL1 enzyme continuously adds phosphate groups
to tyrosine residues on cytoplasmic proteins, activating several
signal transduction pathways. The result is increased clonal proliferation of myeloid cells secondary to a reduction in or
loss of sensitivity to protein regulators.

Question 18

loss of genetic segments in the 59 end of the
ABL1 gene results in an altered protein-binding affinity for
F-actin, which leads to a reduction in contact binding of hema-
topoietic CML cells to stromal cells, causing premature release
of cells into the circulation

Answer 18

F-actin, which leads to a reduction in adhesion = premature release from BM = dysregulate hematopoiesis

Question 19

BCR-ABL1 fusion gene have what time of function

Answer 19

antiapoptotic

Question 20

PBS and BM findings in Person with CMS

Answer 20

• leukocytes with left shift
• thrombocytosis
• extra medullary granulopoeisis in the spleen and liver
• intense hyper cellularity
• megakaryocytes
• pseudo gaucher cells