Haematological Malignancies 1

Module details

Title

Haematological Malignancies 1

Type

Specialist

Module code

SLS429

Credits

10

Requirement

Compulsory

Aim of this module

This module provides trainees with a basic working knowledge of the role of molecular pathology in the diagnosis of haematological malignancies. They are introduced to the current classification of haematological malignancies according to international guidelines (e.g. World Health Organisation, WHO) and the techniques frequently applied within the laboratory. The trainee will acquire the skills required to aid with the management of haematological malignancies, using the myeloproliferative malignancies, chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia  (CLL), classical hairy cell leukaemia and Burkitt lymphoma as exemplars throughout the module; all of the techniques and procedures performed can also apply to other haematological malignancies.

Competencies

#	Learning outcome	Competency	Action
# 1	Learning outcome 1,2,3	Competency  Select the appropriate diagnostic pathway for patients with a suspected diagnosis of the following conditions : CML CLL Ph-negative myeloproliferative malignancies Burkitt lymphoma	Action View
# 2	Learning outcome 2	Competency  Assist with the preparation of samples for analysis, selecting the correct sample processing pathway(s) : CML CLL Ph-negative myeloproliferative malignancies Burkitt lymphoma	Action View
# 3	Learning outcome 3,4	Competency Analyse and interpret appropriate assays for the detection of gene fusions.	Action View
# 4	Learning outcome 3,4	Competency Analyse and interpret genetic analysis for suspected chronic myeloid leukaemia	Action View
# 5	Learning outcome 3,4	Competency Analyse and interpret assays for the detection of gene fusions in lymphoma samples	Action View
# 6	Learning outcome 3,4	Competency Analyse and interpret genetic analysis for Ph-negative myeloproliferative malignancies	Action View
# 7	Learning outcome 3,4	Competency Analyse and interpret genetic analysis for the diagnosis of  chronic lymphocytic leukaemia (CLL)	Action View
# 8	Learning outcome 3,4	Competency Perform and interpret genetic analysis for monitoring of patients with chronic myeloid leukaemia	Action View
# 9	Learning outcome 3,4	Competency Perform and interpret genetic analysis for the identification of sequence variants within tyrosine kinase domains for patients with sub-optimal response to treatment	Action View
# 10	Learning outcome 4,5	Competency Prepare clinical reports for patients being investigated for: myeloproliferative malignancies Burkitt lymphoma chronic lymphocytic leukaemia	Action View
# 11	Learning outcome 1,5	Competency Assist with the preparation of cases to be discussed and reviewed in an MDT meeting with other healthcare professionals	Action View

Assessments

You must complete:

• 2 case-based discussion(s)
• 2 of the following DOPS/ OCEs:

Perform RT-PCR for the detection of the BCR-ABL1 gene fusion	DOPS
Perform FISH for the detection of the BCR-ABL1 gene fusion	DOPS
Analyse the results of molecular genetic tests for the detection of single nucleotide variant (i.e. JAK2 p.V617F; BRAF p.V600E; MPL p.W515L)	DOPS
Perform FISH for the demonstration of a MYC rearrangement in an FFPE derived lymphoma sample	DOPS
Analyse the results of quantitative RT-PCR for monitoring a patient with chronic myeloid leukaemia	DOPS
Prepare a clinical report	DOPS
Discuss patient results with a healthcare professional over the telephone or in person	OCE
Discuss implications of receiving an unlabeled sample with a healthcare professional.	OCE
Participate in an MDT meeting with other healthcare professionals	OCE

Learning outcomes

Using the examples of myeloproliferative neoplasms, chronic myeloid leukaemia,  chronic lymphocytic leukaemiaand Burkitt lymphoma:

1. Interact with relevant disciplines for the diagnosis and treatment of haematological malignancies
2. Apply the appropriate testing strategy that would lead to the diagnosis of a range haematological malignancies
3. Implement the use of appropriate assays for the diagnoses and monitoring of a range of haematological malignancies
4. Interpret the results of appropriate assays for the diagnoses and monitoring of a range of haematological malignancies
5. Prepare clinically relevant interpretative reports of the results of laboratory tests for a range of haematological malignancies

Learning outcomes

Using the examples of myeloproliferative neoplasms (including chronic myeloid leukaemia), chronic lymphocytic leukaemia , classical hairy cell leukaemia and Burkitt lymphoma;

1. Understand the pathogenesis of a range haematological malignancies including the mechanism of activation of oncogenes through genomic variation
2. Classify haematological malignancies as defined by international guidelines eg WHO
3. Describe the laboratory approaches used to diagnose a defined subset of haematological malignancies
4. Summarise the natural history and clinical management of a range haematological malignancies
5. Explain the use of targeted therapies in the treatment of patients
6. Recognise the role of molecular monitoring to assess response to therapy, detection of minimal residual disease, causes of drug resistance and choice of therapy

Indicative content

Pathogenesis of haematological malignancies

• Translocations giving rise to MYC deregulation through IG-MYC
• Translocation giving rise to BCR-ABL1 oncogene (Philadelphia chromosome)
• Pathogenic variants within the myeloproliferative malignancies (including JAK2 p.V617F; CALR and MPL mutations)
• Pathogenic variants within classical hairy cell leukaemia (BRAF p.V600E).
• Molecular consequences of dysregulation of signal transduction pathways in myeloproiliferative malignancies and classical hairy cell leukaemia as a result of mutational processes
• Molecular consequence of MYC activation within lymphoma

 Classification of haematological malignancies (WHO)

• Introduction to the classification of haematological malignancies according to the WHO
• Characteristic features for the diagnosis of Burkitt lymphoma
• Characteristic features for the diagnosis of classical hairy cell leukaemia
• Characteristic features for the diagnosis of the myeloproliferative malignancies (focusing on CML, PV, ET and PMF).
• Introduction to less common myeloid disorders related to the MPNs
  • Chronic neutrophilic leukaemia
  • Mastocytosis
  • Atypical chronic myeloid leukaemia
  • Other tyrosine kinase gene fusions (e.g. PDGFRA; PDGFRB; FGFR1; PCM1-JAK2)
• Introduction to other high grade B cell lymphomas (expanded upon in Year 3)
  • Burkitt-like lymphoma with 11q aberrations
  • High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement

Laboratory approaches for the diagnosis of MPNs, HCL and Burkitt lymphoma

• Characteristic morphology and and/or immunophenotype of each disease
• Appropriate immunohistochemistry and/or flow cytometry techniques approaches
• Use of FISH and G-banding techniques
• Appropriate molecular genetic techniques for the detection of pathogenetic variants
• Sensitivity and specificity of these techniques
• Potential role of next generation sequencing and approaches to assesses copy number variation

Natural history and clinical management of MPNs, HCL and Burkitt lymphoma

• Natural history of the MPNs, HCL and Burkitt lymphoma
• Current approaches to the treatment of MPNs, HCL and Burkitt lymphoma, including targeted therapy
• Mechanism of action of targeted therapies relevant for these disorders

Monitoring of disease

• Definitions of response in CML according to current guidelines
• Use of appropriate BCR-ABL1 quantification techniques for monitoring residual disease
• International guidelines for inter-laboratory comparison of BCR-ABL1 quantification techniques
• Mechanisms of resistance to first line therapy in CML
  • Evaluation of BCR-ABL1 kinase domain mutation
  • Choice of second line therapy
• Appropriate approaches for quantitative monitoring of other relevant mutations (e.g. JAK2 p.V617F; BRAF p.V600E).

Activities

• Attend relevant multidisciplinary team meetings at which the results of the molecular investigations are discussed, along with other laboratory and clinical information Critically reflect on the impact of the laboratory investigations on patient treatment and management
• Attend relevant clinics and review the work of the clinics and interaction with other disciplines (eg Radiology; Haematology)
• Be aware of the sample pathway from the patient to the laboratory and critically reflect on the key stages of the sample pathway from the patient to the laboratory
• Gain experience of and carry out appropriate FISH analysis for the diagnosis of non-complex  haematological malignancies (CML and Burkitt lymphoma)