myeloproliferative disorders

Explain the cause of Chronic Myelogenous leukemia (CML).

The Philadelphia chromosome translocation happens at the t(9;22) swapping portion which leads to the formation of a new gene called BCR-ABL. This gene alteration results in an overactive tyrosine kinase protein that triggers uncontrolled cell growth.

What are some laboratory findings that would point to CML?

• left shift (bands, myelocytes)

• elevated WBC count (all granulocytes are increased)

• increased platelet count

• NRBCs are present

• LAP stain is decreased

What would you see in a bone marrow sample for CML?

• increased cellularity

• increased granulopoiesis

• increased or normal megakaryopoiesis

What treatment would be appropriate for CML?

• bone marrow and stem cell transplantation

• Imatinib mesylate treatment: a synthetic tyrosine kinase inhibitor designed to bind the ATP binding site and this inhibit the tyrosine kinase activity of the BCR/AML fusion protein. It also allows for the cells to go through apoptosis.

Explain the cause of polycythemia vera (PV).

It is caused by the JAK2 mutation. So if a hematopoietic stem cell bears the JAK2 mutation it will be resistant to erythropoietin deprivation apoptosis and will proliferate out of control.

what are some major criteria and minor criteria that could diagnose PV?

Major criteria

• elevated hemoglobin and hematocrit

• identification of the JAK2 V617F mutation

Minor criteria

• panmyelosis in the bone marrow

• low serum erythropoietin

• in vitro erythroid colony formation

peripheral blood findings that indicate PV

• elevated hemoglobin and hematocrit

• normocytic/normochromic erythrocyte morphology

• Mainly RBC count is significantly increased

• WBC increased

• Platelets increased

• Leukocyte alkaline phosphatase (LAP) normal or increased

Bone marrow findings that indicate PV

• normoblasts increased

• granulocytes increased

• megakaryocytes increased

treatment for PV

therapeutic phlebotomy to maintain hematocrit at less than 45%

What are some peripheral blood findings that would indicate Essential thrombocythemia (ET)?

• increased platelet count (greater than 600×10^9/L or sometimes 1000×10^9/L)

• decreased platelet function (not great platelets)

• slightly increased to normal (WBCs) and neutrophils

• normal red blood cells

diagnostic criteria for ET

• platelet count greater than 600×10^9/L (sustained high levels)

• hemoglobin of less than 13 g/dL

• philadelphia chromosome negativity (to diff from CML)

What are some findings in bone marrow that would indicate ET?

• increased megakaryocytes (clusters, large, hyperlobulated, dense nuclei, size variability)

• normal or increased normoblasts

• normal or slightly increased granulocytes

treatment for ET

• prevention or alleviation of hemorrhagic or vasoocclusive complications that occur as platelet count increases

• Alkylating agent hydroxyuria is used to reduce platelet production by the marrow megakaryocyte

what is primary myelofibrosis (PM)?

clonal MPN in which there is splenomegaly and ineffective hematopoiesis associated with areas of marrow hypercellularity, fibrosis, and increased megakaryocytes. it is seen in patients older than age 60 and can be asymptomatic.

peripheral blood findings indicating PM

• immature granulocytes and normoblasts (think polychromasia too)

• dacrocytes (tear drop shaped erythrocytes)

• NRBCs

• decreased hemoglobin

if there is a dry tap (no aspirate), what would that indicate?

dry tap would indicate PM

What is chronic neutrophilic leukemia (CNL)?

Clonal disorder in which a hyperproliferation of neutrophilic cells in the bone marrow produces sustained neutrophilia in the peripheral blood and hepatosplenomegaly.

How can CNL be differentiated from CML?

It can be differentiated by the Philadelphia chromosome and BCR/ABL fusion gene which CNL would be negative for but CML would be positive.

peripheral blood findings indicating CNL

• WBC count of more than 25×10^9/L

• increased neutrophils

• neutrophils can contain toxic granules

• normal RBCs and platelets

Bone marrow findings indicating CNL

• hypercellular with proliferation of neutrophils

• myeloid-to-erythroid ratio is at least 20:1

• RBCs and platelets are normal

• no cell line exhibits significant dysplastic morphology

what is chronic eosinophilic leukemia (CEL)?

clonal proliferation of eosinophils from eosinophil precursors that dominate in the bone marrow and peripheral blood.

why is CEL more serious than CNL?

infiltrating eosinophils degranulate to release cytokines, which result in organ dysfunction (organ failure).