BCR ABL -ve MPNs

Question 1

What is an MPN?

Answer 1

Myeloproliferative Neoplasm.

Proliferation of 1 or more myeloid lineages with normal maturation e.g. increase in number of mature cells.

Question 2

What disorders come under the WHO 2016 classification of MPN?

Answer 2

Chronic neutrophilic leukemia
Polycythemia Vera
Primary Myelofibrosis
Essential Thrombocythemia
Chronic eosinophilic leukemia, not otherwise specified
MPN unclassified

Question 3

In a ?MPN sample, how many cells need to be analysed?

Answer 3

20 cells, but as analysis is usually for the exclusion of Ph then only 5 need to be analysed with the reminder scored (as MPN abnormalities are usually quite obvious).

Question 4

In order to be classified as chronic eosinophilic leukemia, NOS what needs to be carried out?

Answer 4

Need to rule out other disorders where eosinophilia can be part of the picture such as CML (no BCR-ABL)

No rearrangements involving PDGFRA/B or FGFR1

Question 5

What are MPNs generally linked to?

Answer 5

Mutations or rearrangements involving tyrosine kinases.

Question 6

What percentage of MPNs have abnormalities? What abnormalities do you generally see?

Answer 6

None specific myeloid type abnormalities, but rate is quite low.

As disease progresses abnormality rate goes up to 90%.

Abnormalities include; +8, +9, del(5q), del(7q), del(13q), del(20q).

Question 8

What is Polycythemia Vera? What are some general symptoms?

Answer 8

Increase in number of red blood cells.

Symptoms are all related to the increase in RBC. Such as;
Stroke and thrombosis
Headaches 
Dizziness
Visual disturbances

Question 9

What abnormalities are associated with PV?

Answer 9

Cyto abs in up to 20% but nothing specific.

JAK2 mutation in 95%.

Question 10

What percentage of PV transforms into AML?

Answer 10

~20%

Question 11

What is Essential Thrombocythaemia? What are some of the symptoms?

Answer 11

Increase in platelets in the blood and megakaryocytes in the marrow.

Symptoms come from excess of platelets and clotting. Causes blockages which interrupts blood flow - symptoms include thrombosis, bleeding from mucosal surfaces and haemorrhage.

Question 12

What abnormalities are seen in ET?

Answer 12

Only around ~5% have cyto abs.

JAK2 mutation in 63%.

Most important thing is to rule out CML as thromboytosis can be seen in that disorder.

Question 13

What percentage of ET transforms to AML?

Answer 13

<5%

Question 14

What is the median survival of ET?

Answer 14

Good survival at 10-15 years.

Question 15

Where does JAK2 reside?

Answer 15

9p24

Question 16

What is Primary Myelofibrosis?

Answer 16

Fibrosis (scar tissue) of the bone marrow tissue.

Question 17

What percentage of Primary Myelofibrosis cases show cytogenetic abnormalities?

What abnormalities are typically seen?

Answer 17

Approx 60%.

Typically see +8, +9, del(20q), del(13q).

Question 18

What is the role for cyto in MPN?

Answer 18

cyto isn’t essential for diagnosis

report abs as consistent with neoplasia, no comments about prognosis.

No specific cyto abnormalities that will confirm transformation to myelofibrosis or AL but a complex karyotype is strongly suggestive.