Chronic Myeloid Leukemia Overview
37 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which mutation is known as the 'gatekeeper' mutation and displays resistance to all currently available TKIs except ponatinib and asciminib?

  • T315I (correct)
  • ASXL1
  • IKZF1
  • BCR-ABL

    • What categorization does the WHO recommend for CML-AP?

  • Merge it with acute myeloid leukemia
  • Define it based solely on genetic mutations
  • Eliminate it as a distinct entity (correct)
  • Maintain it as a separate disease category

    • Which gene mutations are most frequently associated with progression to CML-BP?

  • FLT3 and CEBPA
  • BCR-ABL and RUNX1
  • ASXL1, IKZF1, and RUNX1 (correct)
  • TP53 and JAK2

    • What is the expected median survival of patients with CML-AP that evolved from CML-CP?

    <p>Less than 3 years</p> Signup and view all the answers

    What treatment option may be less beneficial for patients with somatic variants like ASXL1 mutations?

    <p>Targeted therapy with TKIs</p> Signup and view all the answers

    What is the primary genetic abnormality associated with chronic myeloid leukemia (CML)?

    <p>Translocation involving the ABL1 and BCR genes</p> Signup and view all the answers

    Which of the following best describes the role of the BCR::ABL1 oncoprotein in CML pathogenesis?

    <p>It activates downstream signaling pathways promoting cell growth and survival.</p> Signup and view all the answers

    What is the primary feature of the chronic phase (CP) of CML?

    <p>Increased symptoms of anemia and splenomegaly.</p> Signup and view all the answers

    Which signaling pathway is NOT typically activated by the BCR::ABL1 oncoprotein?

    <p>TGF-β/SMAD</p> Signup and view all the answers

    What percentage of newly diagnosed leukemia cases in adults is accounted for by CML?

    <p>15%</p> Signup and view all the answers

    What is a common clinical finding in patients with chronic myeloid leukemia during diagnosis?

    <p>Presence of the Philadelphia chromosome</p> Signup and view all the answers

    Which treatment approach is emphasized for managing chronic myeloid leukemia?

    <p>Tyrosine kinase inhibitors (TKIs)</p> Signup and view all the answers

    What is the most common symptom experienced by patients in the chronic phase of CML?

    <p>Fatigue due to anemia</p> Signup and view all the answers

    Which symptom is most consistently observed in patients with Chronic Myeloid Leukemia (CML)?

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

    What is the median platelet count observed in about 50% of patients with Chronic Myeloid Leukemia?

    <p>400 × 10^9/L</p> Signup and view all the answers

    What percentage of patients with Chronic Myeloid Leukemia might present with leukocytosis greater than 100 × 10^9/L on diagnosis?

    <p>At least half</p> Signup and view all the answers

    Which laboratory finding is associated with Chronic Myeloid Leukemia in terms of granulocyte presence?

    <p>Presence of hypersegmented neutrophils</p> Signup and view all the answers

    Which of the following conditions is a complication of Chronic Myeloid Leukemia associated with thrombocytosis?

    <p>Gouty arthritis</p> Signup and view all the answers

    In Chronic Myeloid Leukemia, which phase is characterized by an acute leukemia presentation?

    <p>Blast phase</p> Signup and view all the answers

    An increase in absolute basophil count is common in which phase of Chronic Myeloid Leukemia?

    <p>Chronic phase</p> Signup and view all the answers

    What percentage of lymphocytes are expected to be present in the blood of chronic-phase CML patients?

    <p>10% - 15%</p> Signup and view all the answers

    What is the minimum percentage of myeloid blasts in blood or bone marrow to meet the criteria for the blastic phase?

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

    Which laboratory finding is characteristic of chronic myeloid leukemia (CML)?

    <p>M:E ratio greater than 10:1</p> Signup and view all the answers

    What type of PCR is ideal for monitoring residual disease in CML?

    <p>Quantitative PCR</p> Signup and view all the answers

    What hallmark chromosomal abnormality is associated with chronic myeloid leukemia?

    <p>t(9;22)</p> Signup and view all the answers

    Which finding is NOT typically associated with the bone marrow aspiration in CML?

    <p>Marked increase of immature lymphocytes</p> Signup and view all the answers

    How is the BCR::ABL1 gene fusion assessed using FISH analysis?

    <p>By co-localization of genomic probes</p> Signup and view all the answers

    Which finding would indicate the presence of sea-blue histiocytes in the bone marrow?

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

    What is the typical appearance of megakaryocytes in patients with increased numbers in CML?

    <p>Small with hypolobated nuclei</p> Signup and view all the answers

    What is the prevalence of additional chromosomal abnormalities (ACAs) in patients with Ph-positive cells?

    <p>10% - 15%</p> Signup and view all the answers

    Which variant translocation has exhibited a similar response to therapy and prognosis as Ph-positive CML?

    <p>e13a3 or e14a3 variants of p210</p> Signup and view all the answers

    What is the typical translocation seen in 90% of patients with chronic myeloid leukemia (CML)?

    <p>t(9;22)</p> Signup and view all the answers

    Which of the following chromosomal abnormalities is linked to a poor prognosis when detected?

    <p>i(17)(q10)</p> Signup and view all the answers

    What is the range of patients who may present with CML morphologically without Ph-positivity in cytogenetic studies?

    <p>2% - 5%</p> Signup and view all the answers

    Which oncoprotein is produced by the typical BCR::ABL1 e13a2 or e14a2 transcripts?

    <p>p210</p> Signup and view all the answers

    In the differential diagnosis of leukemoid reactions, what is a typical maximum white blood cell count?

    <p>&lt; 50 × 10^9/L</p> Signup and view all the answers

    What would be the potential consequence of not testing for BCR::ABL1 transcripts at diagnosis?

    <p>False impression of complete MR on TKI therapy</p> Signup and view all the answers

    Study Notes

    Definition and Pathogenesis

    • Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm (MPN) caused by a genetic translocation in pluripotent hematopoietic stem cells (HSC).
    • This translocation involves the Abelson murine leukemia (ABL1) gene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22, leading to the formation of a BCR::ABL1 fusion gene.
    • The BCR::ABL1 fusion gene encodes an oncoprotein that acts as a constitutively active tyrosine kinase, promoting CML cell growth and survival.
    • The prevalence of CML is 2 cases per 100,000 individuals.
    • CML accounts for approximately 15% of newly diagnosed leukemia cases in adults, with a slight male predominance.

    Diagnosis and Differential Diagnosis

    • CML diagnosis primarily relies on the presence of the Philadelphia (Ph) chromosome, a t(9;22)(q34;q11) translocation detected by cytogenetics, fluorescence in situ hybridization (FISH), or molecular studies (RT PCR).
    • 90% of patients exhibit the typical t(9;22), while 5% have variant translocations involving chromosome 9 and a chromosome other than chromosome 22 or complex translocations involving multiple chromosomes.
    • Patients with Ph-variants respond to therapy and have a prognosis similar to Ph-positive CML.
    • 2% to 5% of patients present morphologically like CML but are Ph-negative by cytogenetic studies.
    • The typical (BCR::ABL1) e13a2 or e14a2 transcripts produce the oncoproteins p210.
    • A small percentage of patients may exhibit e1a2/a3 transcript (producing p190) or e13a3, e14a3, or e19a2 transcripts (producing p230).

    Clinical Manifestations and Phases

    • CML can be classified into two phases: chronic phase (CP) and blastic phase (BP).
    • Approximately 50% of patients diagnosed with CML are asymptomatic.
    • CML-CP is characterized by symptoms such as fatigue, weight loss, malaise, easy satiety, and left upper quadrant fullness or pain caused by splenomegaly and anemia.
    • CML-BP presents as an acute leukemia, with worsening constitutional symptoms, bleeding, fever, and infections.

    Laboratory Findings

    • Peripheral Blood Smear:
      • Marked granulocytic leukocytosis with left shift, neutrophilia, myelocyte "bulge," basophilia, and absence of increased blasts.
      • Granulocytes lack dysplastic features
    • CBC and Blood Film:
      • Mild to moderate normochromic normocytic anemia with occasional nucleated red blood cells (NRBC). Reticulocyte count is normal or slightly increased.
      • Platelet count is elevated in about 50% of patients.
      • Persistent unexplained leukocytosis, typically greater than 25 × 109/L, with all stages of granulocytes present.
      • Hypersegmented neutrophils are common.
      • Absolute eosinophil count is almost always increased.
      • Absolute basophil count increases in almost all cases.
    • Bone Marrow Aspiration:
      • Hypercellular marrow due to increased myeloid activity.
      • Increased myeloid-to-erythroid ratio (>10:1).
      • Dominant granulopoiesis with broader zones of immature granulocytes.
      • Reduced erythropoiesis.
      • Megakaryocytes are normal or increased in number.
      • Sea-blue histiocytes are present due to marked cell turnover.
    • Bone Marrow Biopsy:
      • Packed marrow with increased numbers of granulocytic cells and megakaryocytes.
      • Marked fibrosis and streaming of hemopoietic cells.

    Treatment and Monitoring

    • Treatment for CML has advanced significantly in recent years, primarily due to the development of tyrosine kinase inhibitors (TKIs).
    • TKIs target the BCR::ABL1 fusion protein, effectively controlling the leukemia.
    • TKI therapy effectively reduces mortality rates to 2–3% annually.
    • Monitoring response to TKIs includes assessing the levels of BCR::ABL1 transcripts in the blood using quantitative PCR (qPCR).
    • Resistance to TKIs can occur, often due to mutations in the BCR::ABL1 gene.
    • Second-generation TKIs, such as ponatinib and asciminib, can overcome resistance to certain mutations, including the T315I mutation.

    References

    • References for the provided information have been omitted in this response.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Chronic Myeloid Leukemia (CML): 2025 Update PDF

    Description

    This quiz covers the definition, pathogenesis, and diagnostic criteria for Chronic Myeloid Leukemia (CML). It explores the genetic factors involved in CML, such as the BCR::ABL1 fusion gene, and details on diagnosis methods like the Philadelphia chromosome. Test your knowledge on this important hematological condition.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser