6-4: Myeloproliferative Disorders

Question 1

What is a myeloproliferative disorder?

Answer 1

neoplastic proliferation of MATURE cells of myeloid lineage (IE - RBC, basophils, eosinophils, neutrophils, megakaryocytes, monocytes)

In this disorder ALL of the above are elevated but specifically the disorder is named based on which one predominates

Question 2

Age group for myeloproliferative disorders?

Answer 2

disease of late adulthood (50-60yr olds)

Question 3

Common complications of myeloproliferative disorders?

Answer 3

• increased risk for hyperuricemia and gout (purine degredation from RBC nucleus for example)
• progression to marrow fibrosis - spent phase
• transformation to acute leukemia

Question 4

Chronic myeloid leukemia

-what cells involved? specifically which one?

Answer 4

• neoplastic proliferation of mature myeloid cells - especially granulocytes
• Basophils are characteristically increased

Question 5

*Basophils are characteristically increased in which disease?

Answer 5

*chronic myeloid leukemia

Question 6

Which translocation drive CML?

What is first line Tx?

Answer 6

• t(9,22) - Philladelphia translocation - BCR-ABL fusion with increased tyrosine kinase activity = overgrowth
• First line treatment is imatinib - blocks tyrosine kinase activity

Question 7

Common symptom in CML? What follows soon after this common symptom?

Answer 7

• splenomegaly –> suggests accelerated phase of disease

- transformation to acute leukemia follows soon after

Question 8

transformation of CML posibilities -

Answer 8

happens after spleen enlarges (accelerated disease) –> acute leukemia EITHER MYELOID or LYMPHOID == MUTATION IS IN A PLURIPOTENT STEM CELL (hematopoetic stem cell is involved)

Question 9

CML vs leukemoid (infection) reaction

Answer 9

• CML granulocytes are LAP (leukocyte alkaline phosphatase) negative - enzyme in secondary granules that deals with inflammation – if infection this enzyme would be present
• CML is associated with inc basophils - basophils usually dont increase with infection
• CML granulocytes exhibit t(9,22 - no translocation with infection)

Question 10

Polycythemia vera-

• proliferation of what cells?
• what mutation?

Answer 10

• proliferation of mature myeloid cells and ESPECIALLY RBC

* -associated wtih JAK2 kinase mutation

Question 11

*JAK2 kinase mutation drives what disease state?

Answer 11

*polycythemia vera

Question 12

Clinical symptoms of Polycythemia vera?

Answer 12

• basically blood bc very thick bc there is so much myeloid based crap in it…
  1) blurry vision and headache
  2) increased risk of venous thrombosis
  3) flushed face due to congestion
  4) itching after bathing

Question 13

Tx of polycythemia vera

Answer 13

• phlebotomy
• secondary Tx = hydroxyurea

-death within one year without Tx

Question 14

Polycythemia vera (PV) vs reactive polycythemia

Answer 14

in PV SaO2 is normal and EPO is decreased

in reactive Polycythemia EPO is increased and SaO2 is low or normal

Question 15

*Tumor that produces EPO?

Answer 15

*renal cell carcinoma

Question 16

Essential thrombocythemia

• proliferation of what cells?
• -what mutation?

Answer 16

• proliferation of mature myeloid cells and ESPECIALLY PLATELETS
• -associated wtih JAK2 kinase (and MPL) mutation

Question 17

A lot of platelets on blood smear could be what diseases?

Answer 17

• iron deficiency anemia

- essential thrombocythemia

Question 18

Essential thrombocythemia

• clinical symptoms?
• progression?

Answer 18

• increased risk of bleeding and/or thrombosis
• Does not progress to marrow fibrosis or acute leukemia
• no significant risk for hyperuricemia or gout (platelets have no nuclear material)

Question 19

Myelofibrosis

• proliferation of what cells?
• -what mutation?

Answer 19

• proliferation of mature myeloid cells, ESPECIALLY MEGAKARYOCYTES
• associated with JAK2 kinase (and MPL) mutation

Question 20

Myelofibrosis - what happens?

Answer 20

-megakaryocytes produce excess PDGF ==> MARROW FIBROSIS

Question 21

No marrow fibrosis vs marrow fibrosis conditions?

Answer 21

NO = essential thromboythemia
YES = myelofibrosis, polycythemia vera (Hairy cell leukemia)

Question 22

Myelofibrosis - clinical features

Answer 22

• splenomegaly due to extramedullary hematopoiesis (bone marrow is no good with fibrosis so production moves to spleen)
• leukoerythroblastic smear (reticulin gates in the bone marrow make sure that blood elements are right size but with fibrosis spleen makes blood components and spleen does not have these gates = all sizes/many immautre forms
• increased risk of infection, thrombosis, and bleeding

Question 23

*Tear drop cells associated with what disease? Why?

Answer 23

• -myelofibrosis -
• when hematopoeisis moves to the spleen but some may still occur in fiBROsed bone marrow == the components squeeze through fibrosis to leave = tear drop shape as they are stretched/stressed