Cytogenetics in Myeloproliferative Neoplasms

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Questions and Answers

What is one of the major criteria for diagnosing Essential Thrombocythemia?

Presence of an autoimmune disorder

Platelet count ≥ 350 X 10⁹/L

Increased levels of reticulin fibers

Platelet count ≥ 450 X 10⁹/L (correct)

Which feature is NOT typically associated with Essential Thrombocythemia?

Vasomotor disturbances

Increased risk of infections (correct)

Splenomegaly in 50% of patients

Thrombotic complications

Which of the following is a cause of reactive thrombocytosis?

Essential Thrombocythemia

JAK-2 mutation

Iron deficiency (correct)

Hypersplenism

What abnormal finding is expected on a blood film in patients suspected of having Essential Thrombocythemia?

Abnormal large platelets Signup and view all the answers

Which mutation is commonly associated with Essential Thrombocythemia?

CALR Signup and view all the answers

What is the main purpose of hydroxyurea in the treatment of conditions associated with elevated platelet counts?

To control platelet count Signup and view all the answers

Which clinical feature is commonly associated with primary myelofibrosis (PMF)?

Massive splenomegaly Signup and view all the answers

Which of the following clinical features is related to thrombotic complications in Essential Thrombocythemia?

Deep vein thrombosis Signup and view all the answers

What is the significance of a bone marrow biopsy in diagnosing Essential Thrombocythemia?

To demonstrate hypercellularity with abnormal megakaryocytes Signup and view all the answers

What laboratory finding is typical in the blood picture of primary myelofibrosis?

Leukoerythroblastic picture Signup and view all the answers

Which of the following is NOT one of the major criteria for diagnosing primary myelofibrosis?

Increased serum iron levels Signup and view all the answers

Which of these conditions is NOT a cause of reactive thrombocytosis?

Essential Thrombocythemia Signup and view all the answers

What percentage of cases show a positive JAK2 mutation analysis in patients suspected of having essential thrombocythemia?

60% Signup and view all the answers

Which feature is characteristic of the red blood cells in primary myelofibrosis?

Tear-drop appearance Signup and view all the answers

Which of the following conditions is associated with failure of aggregation with adrenaline as a laboratory finding?

Essential thrombocythemia Signup and view all the answers

In the course of primary myelofibrosis, which laboratory finding may occur later in the disease progression?

Leukopenia and thrombocytopenia Signup and view all the answers

What is a primary characteristic feature of Essential Thrombocythemia (ET)?

Elevated platelet count Signup and view all the answers

Which of the following is NOT a known cause of reactive thrombocytosis?

Genetic mutation in JAK2 Signup and view all the answers

Which laboratory feature is typically associated with Primary Myelofibrosis?

Leukoerythroblastosis Signup and view all the answers

What treatment option is commonly used for patients with Essential Thrombocythemia?

Interferon therapy Signup and view all the answers

The Philadelphia chromosome is primarily associated with which myeloproliferative disorder?

Chronic Myeloid Leukemia Signup and view all the answers

What type of abnormalities are myeloproliferative disorders primarily classified as?

Acquired clonal abnormalities Signup and view all the answers

Which of the following mutations is often implicated in myeloproliferative neoplasms?

JAK2 mutation Signup and view all the answers

Which of the following describes the typical clinical progression of myeloproliferative disorders?

Can evolve from one subtype to another Signup and view all the answers

Study Notes

Cytogenetics and Molecular Analysis

Analysis of BCR-ABL fusion gene is essential to rule out Chronic Myeloid Leukemia (CML).
JAK2 mutations occur in approximately 60% of relevant cases.
Abnormal platelet function tests show failure to aggregate with adrenaline.

Treatment Aims

Treatment focuses on managing platelet counts and minimizing thrombotic risks.
Hydroxyurea is utilized to control platelet counts (≥ 11 x 10^9/L).

Diagnosis Criteria for Primary Myelofibrosis (PMF)

Diagnosis requires meeting all three major criteria and at least one minor criterion.

Clinical Features of PMF

Insidious onset primarily in older patients, often with anemia symptoms.
Symptoms associated with massive splenomegaly include abdominal discomfort and pain.
Hypermetabolic symptoms such as weight loss, anorexia, fever, and night sweats can manifest.
Additional features may include bleeding, bone pain, and gout.
Splenomegaly is the most significant physical examination finding.

Laboratory Investigations for PMF

Anemia is common; however, some patients may present with normal or elevated hemoglobin levels.
White blood cell and platelet counts are often elevated at the start, leading to leukopenia and thrombocytopenia as the disease progresses.
Characteristic leukoerythroblastic blood picture includes red cells with a "tear-drop" appearance.
Bone marrow may be unobtainable via aspiration ("dry tap"), but biopsies reveal fibrotic, hypercellular marrow and frequent megakaryocytes.
Myelosclerosis (increased bone density) is observed in 10% of cases via X-rays.
Low serum and red cell folate, along with increased serum B12 levels, are notable findings.
Normal NAP score is common; elevated uric acid and LDH levels reflect increased hematopoietic turnover.

WHO Criteria for Essential Thrombocythemia (ET)

Major criteria include platelet count ≥ 450 x 10^9/L and bone marrow biopsy showing proliferation of megakaryocytes without significant left-shift in granulocyte or erythrocyte lineage.
Absence of alternative diagnoses like CML, Polycythemia Vera (PV), PMF, or other myeloid neoplasms is required.
JAK2, CALR, or MPL mutations must be present as part of diagnosis.
Minor criteria include the presence of a clonal marker or absence of reactive thrombocytosis.

Reactive Thrombocytosis Causes

Can stem from iron deficiency, acute or chronic blood loss, hyposplenism or splenectomy, chronic inflammation, various infections, and malignancies.
Rebound thrombocytosis may occur after treatments like ITP or recovery from chemotherapy.

Clinical Features of ET

Vasomotor symptoms may include headaches, visual disturbances, dizziness, and paresthesias.
Thrombotic manifestations can affect arteries (e.g., TIA, CVA) and veins (e.g., deep vein thrombosis, mesenteric).
Hemorrhagic events may occur in gastrointestinal and urogenital pathways.
Obstetric complications include spontaneous abortion and premature delivery.
Splenomegaly reported in about 50% of patients.

Laboratory Investigations for ET

Blood films reveal abnormally large platelets and megakaryocyte fragments.
Bone marrow trephine biopsy displays hypercellular marrow packed with abnormal megakaryocytes.

General Considerations for Myeloproliferative Neoplasms (MPNs)

MPNs arise from acquired clonal abnormalities in hematopoietic stem cells.
There are qualitative and quantitative changes in myeloid, erythroid, and platelet cell lines.
These disorders often have overlapping clinical and laboratory features and can evolve from one type to another.
Progression to Acute Myeloid Leukemia (AML) is a potential outcome of these conditions.
Common pathogenic mechanism involves constitutive tyrosine kinase activation.
The Philadelphia chromosome was the first identified cytogenetic abnormality in human malignancy linked to CML.
Genetic advances have revealed mutations in genes like JAK2, MPL, CALR, and CSF3R among MPNs.

JAK2 Gene Function

JAK2 gene encodes a protein that is instrumental in promoting cell growth and division.

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Description

This quiz covers critical aspects of cytogenetics and molecular analysis relevant to myeloproliferative neoplasms, specifically focusing on the BCR-ABL fusion gene and JAK2 mutation analysis. Additionally, it addresses treatment options and diagnosis indicators like platelet function tests and splenomegaly. Test your understanding of these concepts and their implications for patient management.