Chronic Myeloid Leukaemia
Page 3: Learning Objectives
Review of haematopoiesis.
Identify clinical and laboratory characteristics of CML.
Discuss molecular biology of the Philadelphia (Ph) Chromosome.
Understand the mechanism of tyrosine kinase inhibitors (TKIs).
Examine treatment monitoring systems for CML.
Page 5: Haematopoiesis Overview
Prenatal and Postnatal Haematopoiesis:
Yolk sac (foetal) → Bone marrow (postnatal).
Page 6: Haematopoiesis Cell Types
Hematopoietic Stem Cells: Multipotent origin.
Differentiation pathways include:
Myeloid Progenitors: Erythrocytes, platelets.
Lymphoid Progenitors: T and B lymphocytes, natural killer cells.
Key cell types include myeloblast, lymphoblast, and various progenitor cells.
Page 7: Morphology of White Blood Cells
Overview and normal proportion of white blood cells:
Neutrophils (62%), Lymphocytes (30%), Monocytes (5%), Eosinophils (2.5%), Basophils (0.75%).
Page 9: Mutations in Haematopoiesis
Clonal haematopoiesis and its evolution through various factors: aging, inflammation, environmental impacts.
Specific mutations associated with hematologic neoplasms include DNMT3A, TET2.
Page 10: Classification of Blood Cancers
Liquid Tumours:
Leukaemia: Chronic, Acute.
Multiple Myeloma, Myelodysplasia.
Solid Tumours:
Hodgkin's and Non-Hodgkin's Lymphoma.
Page 11: Chronic Myeloid Leukaemia (CML) Characteristics
A clonal myeloproliferative disorder affecting myeloid cells.
Key features include high myelocyte percentage & neutrophils in bone marrow.
Stats: 15-20% of all leukaemia cases, more frequent in ages 65+, slight male predominance.
Page 13: CML Risk Factors
Involves ionizing radiation exposure, chemicals (e.g., benzene, cigarettes), immunodeficiency, also genetic predispositions based on age and sex.
Page 14: Overview of Earlier Studies on CML
Previous findings have linked environmental factors with increased risks of leukaemia, emphasizing the role of exposures to harmful substances.
Page 15: CML Incidence and Outcome Statistics
Approx.: 9,110 new cases in the UK per year, ~1,220 deaths.
Survival Rates: Variations based on age and gender.
Page 16: Common Symptoms of CML
Symptoms include unexplained fever, anaemia, headaches, frequent infections, and more.
Page 17: Detailed Clinical Symptoms of CML
Additional symptoms include night sweats, abdominal pain, and splenomegaly.
Page 18: CML Pathophysiology
First leukaemia linked to a genetic mutation (Philadelphia Chromosome, Ph).
95% of CML patients harbour this translocation (9;22).
Page 20: Role of Tyrosine Kinases in CML
Define tyrosine kinases and their role in signaling pathways.
Mutations leading to sustained activity linked directly to cancer progression.
Page 21: Mechanism of Tyrosine Kinase Activation
Discusses ligand interactions and spontaneous dimerization.
Page 22: BCR-ABL Protein Structure
Diagram illustrating functions of BCR and ABL components.
Page 23: Diagnosis of CML
Initial evaluation includes blood tests, morphology, and cytogenetic analysis.
Critical for accurate classification and treatment planning.
Page 24: Detailed CML Diagnostic Criteria
Lab results typically show elevated WBC and low red blood cells and platelets.
Page 25: Additional Diagnostic Information
Further elaboration on diagnostic testing methods and clinical implications.
Page 26: Phases of CML
Characteristic durations and symptoms associated with each phase: Chronic, Accelerated, and Blast Crisis.
Page 27: Characteristics of Blast Crisis
Describes acute transformation indicating high blast percentages and treatment challenges.
Page 28: Future Treatments for CML
References to CRISPR and potential gene therapies being explored.
Page 29: Treatment Options for CML
Diverse strategies including targeted therapies, stem cell transplantation, chemotherapy, and supportive care.
Page 30: Details on Targeted Therapy for CML
Involves the use of tyrosine kinase inhibitors (TKIs) to manage cancer progression.
Page 31: Recent Studies on TKIs
References and studies examining combined therapies for improved CML outcomes.
Page 32: Specificity of Imatinib Efficacy
Imatinib hailed as groundbreaking therapy approved in 2001, maintaining BCR-ABL inhibition and delaying progression.
Page 33: Additional References on Imatinib Development
Continuation of discussions about targeting leukaemia therapies.
Page 34: Resource Reference for CML Explanation
Cited reference sources offer foundational knowledge in hematology.
Page 35: Continuation of Essential References for CML
Further bibliographic material relevant for understanding CML.
Page 36: Chemotherapy Overview for CML
Mechanisms of drugs utilized and their induction of apoptosis in leukemic cells.
Page 37: Clinical Trials for CML Treatments
Ongoing investigations include combinations of TKIs and traditional chemotherapy.
Page 38: Chemotherapy Side Effects
Notable toxicities associated with CML treatments impacting various organ systems.
Page 39: Multi-Drug Resistance (MDR) in CML
Definition and implications of MDR on treatment efficacy.
Page 40: Mechanisms Underlying MDR in CML
Detailed discussion on genetic factors influencing drug resistance.
Page 41: Stem Cell Transplantation for CML
Highlighted as a curative option for patients resistant to TKIs.
Page 42: Graft Versus Leukaemia Effect in CML
Importance of immune response post-transplant in achieving remission.
Page 43: Challenges in Stem Cell Transplantation
Discusses complications such as graft rejection and infections.
Page 44: Graft Versus Host Disease (GvHD)
Summary of GvHD implications post-transplant and related management strategies.
Page 45: Active vs Inactive GvHD Indications
Visual demonstration of active and inactive symptoms.
Page 46: Pre-Transplant Considerations for CML
Description of pertinent issues before eligibility for stem cell transplantation.
Page 47: Supportive Therapy for CML Patients
Therapeutic measures aimed at alleviating symptoms and side effects.
Page 48: Treatment Monitoring and Adjustments
Highlights how treatment effectiveness is assessed through various methodologies.
Page 49: Definitions of CML Treatment Responses
Explanation of response criteria as it relates to TKI therapy over time.
Page 50: Suggested Further Readings on CML
Recommendations for in-depth studies concerning CML advancements.
Page 51: Additional References for CML Studies
Extended literature for comprehensive understanding of CML dynamics.
Page 52: Conclusion and Feedback Section
Invitation for feedback on lecture material, possible improvements noted.