Myeloid Flashcards
What is Chronic Myeloid Leukemia (CML)?
A clonal myeloproliferative neoplasm characterized by uncontrolled proliferation of myeloid cells in the bone marrow and their accumulation in the blood.
Most commonly associated with the Philadelphia chromosome (Ph), resulting in the BCR-ABL1 fusion gene, a constitutively active tyrosine kinase.
What chromosome translocation is associated with CML?
t(9;22)(q34;q11)
This translocation results in the BCR-ABL1 fusion gene.
What are common symptoms of CML?
- Fatigue
- Weight loss
- Night sweats
- Early satiety due to splenomegaly
- Signs of anemia or thrombocytosis
Symptoms often present in the chronic phase.
What laboratory finding is characterized by leukocytosis in CML?
Leukocytosis (often >100 x 10⁹/L)
Accompanied by neutrophilia with left shift, basophilia, and eosinophilia.
What does a peripheral blood smear show in CML?
Shows granulocytic precursors at various stages.
Confirms the differential diagnosis.
What is indicated by hypercellularity in a bone marrow biopsy for CML?
Increased myeloid:erythroid ratio
Blasts <10% in chronic phase.
What is the role of karyotyping in CML diagnosis?
Identification of the Philadelphia chromosome (t(9;22)).
How does FISH testing contribute to CML diagnosis?
Detects BCR-ABL1 fusion gene in interphase cells.
What does RT-PCR quantify in CML monitoring?
Quantifies BCR-ABL1 transcripts; used for ongoing monitoring.
What is the goal of monitoring response to therapy in CML?
To evaluate the effectiveness of tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, or nilotinib.
Define Hematologic Response (HR) in CML monitoring.
Normalization of blood counts and spleen size.
What characterizes a Complete Cytogenetic Response (CCyR)?
0% Ph+ cells.
What is Major Molecular Response (MMR) in CML?
BCR-ABL1 ≤0.1% (3-log reduction).
What is the monitoring schedule for qPCR in CML?
Every 3 months until MMR is achieved, then every 3–6 months if stable.
What is monitored at the 3-month milestone according to ELN Guidelines?
BCR-ABL1 ≤10% or CCyR.
Warning: BCR-ABL1 >10%.
What indicates treatment failure in CML monitoring?
Loss of response or mutation conferring TKI resistance.
Fill in the blank: The BCR-ABL1 fusion gene results from a translocation between chromosomes _____ and _____.
9, 22
What are the three groups of CML patients defined by the ELN guidelines based on molecular response milestones?
- Optimal response
- Warning
- Failure
These classifications are based on the achievement of cytogenetic and/or molecular milestones during treatment.
What defines Early Molecular Response (EMR) in CML treatment?
Achievement of a BCR-ABL1 international scale (IS) transcript level < 10% after 3 months of therapy
EMR indicates a reduction of at least 1 log of BCR-ABL1 transcript levels from the standardized IS baseline.
How does Early Molecular Response (EMR) influence CML patient outcomes?
It predicts the outcome, influencing event-free survival (EFS), progression-free survival, and overall survival
EMR is crucial for patients receiving imatinib or second generation TKI.
What is the second molecular milestone in CML treatment?
BCR-ABL1 IS transcript level < 1% after 6 months of therapy
This milestone represents a 2 log reduction in BCR-ABL1 transcript levels.
What does MMR stand for in the context of CML treatment?
Major Molecular Response
MMR consists of a reduction of the BCR-ABL1 transcript level by at least 3 logs (MR3) after 12 months.
What is required for trials of treatment discontinuation in CML patients?
Achievement of a stable deep molecular response defined as a 4-log reduction in tumour load sustained for at least a year
This is measured by qRT-PCR adjusted to the international scale (IS) with BCR::ABL1IS ≤ 0.01%.
