Medicine Marrow Pg 111-120 (Hematology)
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Questions and Answers

What is the most common mutation associated with Essential Thrombocytosis (ET)?

  • MPL mutation
  • CALR mutation
  • JAK-2 mutation (correct)
  • None of the above

    • Essential Thrombocytosis has a higher risk of conversion to Myelofibrosis compared to Polycythemia Vera.

    False

    What age group is most commonly affected by Essential Thrombocytosis?

    50-60 years

    In Essential Thrombocytosis, the platelet count is greater than _____ Lakhs.

    <p>4.5</p> Signup and view all the answers

    Match the following complications and their associated risks of conversion:

    <p>Essential Thrombocytosis = Least risk of conversion Polycythemia Vera = Highest risk of conversion Primary Myelofibrosis = Middle risk of conversion</p> Signup and view all the answers

    What is a key feature in the diagnosis of myeloproliferative neoplasms?

    <p>Normal RBC and WBC counts</p> Signup and view all the answers

    A sustained platelet count greater than 4.5 lakhs is indicative of reactive thrombocytosis.

    <p>False</p> Signup and view all the answers

    What is the primary mutation considered in the treatment algorithm for myeloproliferative neoplasms?

    <p>JAK-α mutation</p> Signup and view all the answers

    In low-risk management of myeloproliferative neoplasms, the first-line treatment is ______.

    <p>Aspirin</p> Signup and view all the answers

    Match the following treatments with their effectiveness in low-risk myeloproliferative neoplasms:

    <p>Aspirin = First-line treatment Hydroxyurea = Second-line treatment Interferon = Third-line treatment Anagrelide = Least preferred option</p> Signup and view all the answers

    Which chromosome is associated with the BCR gene?

    <p>Chromosome 22</p> Signup and view all the answers

    The Philadelphia (Ph) chromosome is present in 50% of chronic myeloid leukemia cases.

    <p>False</p> Signup and view all the answers

    What is the result of the BCR-ABL translocation in chronic myeloid leukemia?

    <p>Constitutively activated ABL kinase</p> Signup and view all the answers

    The process of myelopoiesis involves the transformation of myeloblasts into __________.

    <p>mature neutrophils</p> Signup and view all the answers

    Match the genetic components with their associated features:

    <p>ABL gene = Located on chromosome 9 BCR gene = Located on chromosome 22 Philadelphia chromosome = Shortened long arm of chromosome 22 Myristoyl binding site = Absent in translocation</p> Signup and view all the answers

    What does an elevated Tryptase level indicate?

    <p>Diagnosis of hematological neoplasm</p> Signup and view all the answers

    A low LAP score is associated with conditions such as PNH and CML.

    <p>True</p> Signup and view all the answers

    What is the significance of conventional karyotyping in CML?

    <p>To rule out abnormalities such as double Philadelphia chromosome and trisomy 8.</p> Signup and view all the answers

    In the bone marrow study for CML, it is important to quantify __________.

    <p>blasts</p> Signup and view all the answers

    Match the following tests with their purposes:

    <p>Peripheral Smear = Identify anemia and leukocytosis Flow Cytometry = Determine cell characteristics FISH = Detect BCR-ABL gene Molecular Genetics = Quantitative analysis of BCR-ABL</p> Signup and view all the answers

    What is the recommended dose of Imatinib for a chronic phase?

    <p>400 mg</p> Signup and view all the answers

    A complete cytogenic response (CCR) indicates the presence of the Philadelphia chromosome in the bone marrow.

    <p>False</p> Signup and view all the answers

    Name one tyrosine kinase inhibitor used for treating chronic phases.

    <p>Imatinib</p> Signup and view all the answers

    The primary goal of using hydroxyurea is to ↓ cell _______.

    <p>turnover</p> Signup and view all the answers

    Match the following tyrosine kinase inhibitors with their respective doses:

    <p>Imatinib = 400 mg Nilotinib = 300 mg BID Dasatinib = 100 mg/day Ponatinib = 45 mg/day</p> Signup and view all the answers

    What is one of the major criteria for diagnosing myeloproliferative neoplasms?

    <p>Hb: &gt;16.5 g/dL in men and &gt;11.6 g/dL in women</p> Signup and view all the answers

    A subnormal serum erythropoietin level is considered a minor criterion for the diagnosis of myeloproliferative neoplasms.

    <p>True</p> Signup and view all the answers

    Name one mutation associated with primary myelofibrosis.

    <p>JAK-2 mutation</p> Signup and view all the answers

    In low-risk management of myeloproliferative neoplasms, patients are advised to undergo ______ and take aspirin.

    <p>phlebotomy</p> Signup and view all the answers

    Match the following mutations associated with primary myelofibrosis to their prevalence:

    <p>JAK-2 mutation = 50% Calreticulin (CALR) = 30-40% MPL gene mutation = 10-20% Triple negative PMF = Poor prognosis</p> Signup and view all the answers

    What characteristic is typically seen in a peripheral smear of a patient with myeloproliferative neoplasms?

    <p>Leukoerythroblastosis with teardrop red cells</p> Signup and view all the answers

    A dry tap on bone marrow aspirate is a common finding in myeloproliferative neoplasms.

    <p>True</p> Signup and view all the answers

    What is the median survival for patients with myeloproliferative neoplasms?

    <p>5 years</p> Signup and view all the answers

    Peripheral smear may show ____________, which includes immature myeloid cells and nucleated red blood cells.

    <p>leukoerythroblastosis</p> Signup and view all the answers

    Match the following types of megakaryocytes with their associated conditions:

    <p>Staghorn = Essential Thrombocytosis (ET) Dwarf = Chronic Myeloid Leukemia (CML) Giant = Immune Thrombocytopenic Purpura (ITP)</p> Signup and view all the answers

    What is a common clinical feature of chronic myeloproliferative neoplasm in the chronic phase?

    <p>Asymptomatic leukocytosis</p> Signup and view all the answers

    Blast crisis in myeloproliferative neoplasms is characterized by more than 20% blasts in the blood or marrow.

    <p>True</p> Signup and view all the answers

    What is the typical 5-year survival rate for patients with chronic myeloproliferative neoplasms?

    <p>85-90%</p> Signup and view all the answers

    ___ is a common consequence of high cell turnover in myeloproliferative neoplasms, leading to joint issues.

    <p>Acute gouty arthritis</p> Signup and view all the answers

    Match the following symptoms with their associated conditions or effects:

    <p>Massive splenomegaly = Extramedullary hematopoiesis Fatigue = Anemia due to cytokines Unexplained fever = Blast crisis High white blood cell count = Asymptomatic leukocytosis</p> Signup and view all the answers

    What is a characteristic clinical feature observed in myeloproliferative neoplasms?

    <p>Massive splenomegaly</p> Signup and view all the answers

    Pancytopenia in myeloproliferative disorders can lead to fatigue, bleeding, and gout.

    <p>True</p> Signup and view all the answers

    What skin condition is characterized by febrile neutrophilic dermatosis?

    <p>Sweet syndrome</p> Signup and view all the answers

    Individuals over _____ years old are primarily affected by myeloproliferative neoplasms.

    <p>60</p> Signup and view all the answers

    Match the following clinical features with their associated conditions:

    <p>Thrombosis = Increased risk in PCRV &gt; ET &gt; PMF B-Symptoms = Fever, night sweats, weight loss Pancytopenia = Anemia, bleeding, gout Skin lesions = Febrile neutrophilic dermatosis</p> Signup and view all the answers

    Which of the following findings is noted in the bone marrow aspirate of myeloproliferative neoplasms?

    <p>Predominant granulopoiesis</p> Signup and view all the answers

    Increased dwarf megakaryocytes is a finding in myeloproliferative neoplasms.

    <p>True</p> Signup and view all the answers

    What is the significance of the presence of sea blue histiocytes in myeloproliferative neoplasms?

    <p>They are indicative of Gaucher cells.</p> Signup and view all the answers

    In the accelerated phase of myeloproliferative neoplasms, basophilia is defined as greater than _____%.

    <p>20</p> Signup and view all the answers

    Match the following prognostic scales with their elements:

    <p>Hasford Prognostic Scale = Circulating blasts Sokal Index = Platelet count Age = Hasford Prognostic Scale Eosinophils and basophils in blood = Hasford Prognostic Scale</p> Signup and view all the answers

    Study Notes

    Chronic Myeloid Leukemia

    • Pathophysiology:
      • Myeloid cells: eosinophil, basophil, RBC, platelets, monocyte.
      • Myelopoiesis: myeloblast → promyelocyte → myelocyte → metamyelocyte → band forms → segmented forms → mature neutrophils.
      • Molecular genetics: Long arm of chromosome 9 (ABL gene).
      • Molecular genetics: Long arm of chromosome 22 (BCR gene).
      • BCR-ABL fusion gene: Created by a translocation between chromosomes 9 and 22.
      • Philadelphia (Ph) chromosome: Shortening of the long arm of chromosome 22.
      • Constitutively activates ABL kinase: This activation is a result of the translocation.
      • Act as a docking site of ATP: This change is caused by the translocation.
      • Tyrosine phosphorylation: Occurs because of the above changes.

    Essential Thrombocytosis (ET)

    • Benign disease: Typically has a good prognosis.
    • Etiology:
      • JAK-2 mutation (50-60%)
      • CALR mutation (30-40%)
      • MPL mutation (10-20%)
    • Clinical features:
      • Mild splenomegaly
      • Thrombosis (due to hyperplasia)
      • Bleeding (due to dysplastic cells)
      • Female > Male
      • Age: 50-60 years
    • Investigations:
      • RBC: Normal
      • WBC: Normal
      • Platelet count (PLC): >4.5 lakhs
      • Bone marrow biopsy: Megakaryocytes show hyperplasia (few dysplastic)
      • Staghorn cells: Giant cells with mature cytoplasm, hyperlobulated nuclei.
    • Management:
      • Low Risk: Aspirin, Hydroxyurea, interferon, anagrelide.
      • High Risk: Hydroxyurea, Ruxolitinib.
    • Complications:
      • Myelofibrosis
      • AML (Acute myeloid leukemia) (PCRV > PMF > ET)
    • Note: PCRV stands for Polycythemia vera, PMF for primary myelofibrosis.

    CML Management

    • Investigations:
      • Peripheral smear:
        • RBC: Anemia
        • WBC: Increased (1 lakh)
        • Blast forms: Less than 5%
        • Myelocyte (maximum): Myelocyte bulge
        • All stages seen
        • Eosinophilia
        • Basophilia
        • Thrombocytosis (No hemorrhage/thrombosis)
      • LAP (Leukocyte Alkaline Phosphatase): Low (Cytochemical abnormal WBC)
      • Tryptase: Increased
      • Bone marrow study:
        • Conventional karyotyping (mandatory): To rule out abnormalities (Double ph, trisomy 8, isochromosome 17, Deletion of 20q)
        • Quantify blasts.
        • To determine degree of fibrosis.
    • Current methods:
      • Chronic phase + second abnormality → Bad prognosis (Double PH, isochrome 17, trisomy 8)
      • All other conditions: Prognosis assessment after Rx (TKI).
    • Management:
      • Hydroxyurea: To ↓ cell turnover
      • Tyrosine Kinase inhibitors (TKIs):
        • Imatinib (Gleevec): 400 mg: Chronic phase. 600-800 mg: Blast crisis.
        • Bosutinib: 500 mg/day
        • Nilotinib: 300 mg BID
        • Dasatinib: 100 mg/day
        • Ponatinib: 45 mg/day
        • Asciminib: -

    Primary Myelofibrosis (PMF)

    • Etiology:
      • JAK-2 mutation: 50%
      • Calreticulin (CALR): 30-40%
      • MPL gene mutation (Codes for thrombopoietin): 10-20%
      • Triple negative PMF: Absence of above mutations (Poor prognosis)
      • Deletion 13q.
    • Clinical Features:
      • Age: Primarily over 60 years old.
      • Gender: Male and female equally affected.
      • Thrombosis: Increased risk in cases of PCRV > ET > PMF.
      • B-Symptoms (20%): Fever, night sweats, weight loss.
      • Pancytopenia:
        • Anemia: Fatigue is a common symptom.
        • Bleeding
        • Gout: During proliferation stage.
        • Extramedullary hematopoiesis
        • Osteosclerosis
      • Skin: Febrile neutrophilic dermatosis (Sweet syndrome)
      • Organs: Massive splenomegaly (75%) and hepatomegaly (portal hypertension).
    • Investigations:
      • Peripheral smear:
        • Leukoerythroblastosis (immature myeloid cells CD34+, nucleated red cells)
        • Anisocytosis and poikilocytosis with teardrop red cells (dacryocytes)
        • Thrombocytosis: Cloud-like megakaryocytes
      • Serum type-III procollagen peptide: Increased
      • Bone marrow aspirate: Dry tap
      • Bone marrow biopsy:
        • Silver impregnation: Reticulin fibrosis + collagen fibrosis
        • Fibrosis with hypercellular marrow
    • Management:
      • Medical treatment:
        • Oral Ruxolitinib: In JAK-2 mutation
        • Lenalidomide
      • Definitive treatment:
        • Allogenic hematopoietic stem cell transplant (AHSCT)
        • Limitations: Complete match required, Increased risk of infection.
    • Complications:
      • Transformation to AML: 10-20%

    Polycythemia Vera (PCRV)

    • Diagnosis: WHO criteria → 3 major (or) a major + 1 minor criteria.
      • Major criteria:
        • Hb: >16.5 g/dL in men and >11.6 g/dL in women.
        • Bone marrow: Hypercellularity.
        • JAK-2 mutation.
      • Minor criteria: Subnormal serum erythropoietin level.
    • Management:
      • Low risk: Phlebotomy + Aspirin 75 mg + JAK inhibitor: Ruxolitinib 10 mg BD or Hydroxyurea: 0.5-2 g/day.
    • Prognosis:
      • Hasford Prognostic Scale:
        • Circulating blasts
        • Spleen size
        • Platelet count
        • Age
        • Eosinophils and basophils in blood
      • Sokal Index
    • Clinical Features:
      • Symptomatic: Headaches, fatigue, dizziness, tinnitus, blurry vision, night sweats, pruritis.
    • Investigations:
      • Bone Marrow Aspirate:
        • Marked hypercellularity
        • Predominant granulopoiesis (30:1)
        • Erythropoiesis: Decreased
      • Other Findings:
        • Megakaryocytes (Dwarf): Increased
        • Sea blue histiocytes (Gaucher cells): Present
        • Fibrosis: Increased
    • Peripheral smear:
      • Erythrocytosis: Increased RBC count
      • Hypersegmentation of neutrophils
      • Basophilia
      • Thrombocytosis

    Chronic Myeloid Leukemia (CML)

    • Risk factors:
      • Age: 50-60 years
      • Gender: Male > Female
      • High dose ionizing radiation (6-8 years)
      • Germ line susceptibility: very low
    • 5-Year Survival Rate: 85-90%
    • Clinical Features:
      • Chronic Phase:
        • Asymptomatic leukocytosis (WBC ~ 1 lakh):
          • Fatigue due to anemia
          • Massive splenomegaly: abdominal distension, left upper quadrant and shoulder pain, early satiety
        • Loss of appetite
        • Acute gouty arthritis: Hyperuricemia (↑ cell turnover)
        • Acne/urticaria/pruritis: ↑ basophils (Histamine release)
        • B-symptoms (10-15%): Fever, weight loss, night sweats.
      • Blast Crisis:
        • Blast ≥20% in blood/marrow
        • Present in untreated cases within 4 years.
        • Extramedullary blast proliferation
        • Unexplained fever
        • Bone pain
        • Bleeding (↓ PLC)
    • Note:
      • B-symptoms: Classically seen in Hodgkin's disease.
      • If WBC > 2 lakh: Symptoms of hyperviscosity (headache, blurring of vision, priapism, vertigo).
    • Pathogenesis:
      • Myeloproliferation (Hypercellular marrow): Dysplastic megakaryocytes (lack CXCR4 receptors) lead to marrow fibrosis (increased type-III collagen).
      • Release of precursor cells: Leads to leukoerythroblastosis in the peripheral smear.
    • Management:*
      • Tyrosine kinase inhibitors (TKIs):
        • Act on MBS.
        • Imatinib, Asciminib.
    • Prognosis:
      • Hasford Prognostic Scale:
        • Circulating blasts
        • Spleen size
        • Platelet count
        • Age
        • Eosinophils and basophils in blood
      • Sokal Index
    • Miscellaneous
      • Marrow 8.0
      • 2024
      • Scanned with OKEN Scanner

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    Description

    This quiz covers the pathophysiology and molecular genetics of Chronic Myeloid Leukemia (CML) and Essential Thrombocytosis (ET). Key topics include myelopoiesis, BCR-ABL fusion gene, and the various mutations associated with ET. Test your knowledge on these hematological conditions.

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