Haematological Malignancies: Aetiology & Genetics

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is a characteristic feature of deletions in chromosomes?

Addition of extra chromosomes

Complete duplication of the chromosome

Partial loss of a chromosome segment (correct)

Transformation of the chromosome structure

Which of the following techniques involves direct morphological analysis of chromosomes?

Polymerase Chain Reaction (PCR)

Karyotyping (correct)

Flow cytometry

Immunohistochemistry

Which chromosomal alteration is referred to as 'hypodiploidy'?

Loss of multiple chromosomes (correct)

Duplication of chromosomes

Gain of an entire chromosome

A specific mutation in a single gene

What is the purpose of polymerase chain reaction (PCR) in genetics?

To amplify specific DNA segments Signup and view all the answers

Flow cytometry can detect tumor cells by analyzing what aspect?

Surface antigen expression patterns Signup and view all the answers

What type of cells are usually examined in immunohistochemistry?

Tumor tissue sections Signup and view all the answers

Which of the following chromosome numbers indicates potential monosomy?

45 chromosomes Signup and view all the answers

Colchicine is used in karyotyping to?

Arrest cells in metaphase Signup and view all the answers

What type of diseases are haematologic malignancies classified as?

Clonal diseases Signup and view all the answers

Which of the following is NOT a component of haematologic malignancies?

Carcinomas Signup and view all the answers

What percentage of all cancers do haematologic malignancies represent?

7% Signup and view all the answers

Which genetic disease is associated with a higher incidence of haematologic malignancies?

Down’s syndrome Signup and view all the answers

Which of the following environmental factors is linked to an increased risk of haematologic malignancies?

Exposure to benzene Signup and view all the answers

What is a primary characteristic of haematologic malignancies regarding their origin?

They derive from a single cell. Signup and view all the answers

Which of the following conditions shows a weak familial tendency for haematologic malignancies?

Chronic lymphocytic leukaemia (CLL) Signup and view all the answers

Which of the following statements about environmental factors in haematologic malignancies is inaccurate?

Only chemicals are considered environmental factors. Signup and view all the answers

What is the result of exposure to environmental factors like radiation and drugs?

Proliferation of aberrant cells Signup and view all the answers

Which virus is associated with Adult T-cell leukaemia lymphoma (ATLL)?

Human T-lymphotropic virus type 1 (HTLV-1) Signup and view all the answers

What causes a proto-oncogene to transform into an oncogene?

Duplication and gain-of-function mutation Signup and view all the answers

What is translocation in the context of genetic mutations?

Exchange of genetic material between non-homologous chromosomes Signup and view all the answers

Which of the following contributes to the formation of a chimeric fusion gene?

Translocation of genetic material Signup and view all the answers

What is the primary outcome of genetic mutations accumulating in cellular genes?

Malignant transformation Signup and view all the answers

Which infective agent is linked to Mucosa Associated Lymphoid Tissue (MALT) lymphoma?

Helicobacter pylori Signup and view all the answers

What process is described as a good cop becoming a bad cop in genetics?

Transformation of proto-oncogenes to oncogenes Signup and view all the answers

What is the result of the BCR-ABL1 fusion gene in Chronic Myeloid Leukaemia?

It codes for a fusion protein that causes excessive tyrosine kinase activity. Signup and view all the answers

Which chromosomal translocation is associated with the over-expression of the BCL-2 gene?

t(14;18) Signup and view all the answers

What is a common example of a chromosomal duplication seen in Chronic Lymphocytic Leukaemia (CLL)?

Trisomy 12 Signup and view all the answers

What process often results in tumor suppressor genes turning into cancer-causing genes?

Point mutations Signup and view all the answers

Which gene is commonly known as a tumor suppressor gene that regulates the cell cycle?

p53 Signup and view all the answers

What is the outcome of chromosomal duplication?

Extra genetic activity resulting from additional chromosome segments. Signup and view all the answers

What type of genetic mutation involves changing a single nucleotide base?

Point mutation Signup and view all the answers

Which gene fusion is associated with acute myeloid leukaemia through the t(15;17) translocation?

RARα-PML Signup and view all the answers

What is the primary use of fluorescent in situ hybridization analysis?

To detect extra copies of genetic material Signup and view all the answers

What is the role of reverse transcriptase in the DNA microarray platform?

To convert mRNA to ds-cDNA Signup and view all the answers

Which technique is described as Next Generation Sequencing?

Gene Sequencing Signup and view all the answers

Which of the following viruses is linked with Kaposi sarcoma?

Human herpes-8 Signup and view all the answers

Which method is NOT typically used to study haematological malignancies?

High liquid performance chromatography Signup and view all the answers

Which statement regarding oncogenes is false?

Derived following a loss of function of proto-oncogenes Signup and view all the answers

What aspect do the diagnostic techniques in haematological malignancies primarily aid in?

Aiding early diagnosis and treatment decisions Signup and view all the answers

Which of the following statements is true regarding fluorescent-labelled probes?

They hybridize to specific parts of the genome Signup and view all the answers

Study Notes

Haematological Malignancies: Aetiology and Genetics

Haematological malignancies are clonal diseases affecting the haemopoietic tissues.
They originate from a single cell in the bone marrow or peripheral lymphoid tissues.
Often, the tissue of origin has pre-existing genetic alterations.
Common types include leukaemias, lymphomas, myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN).

Synopsis

The presentation covers introduction, epidemiology, aetiology, genetics, diagnostic techniques in haemato-oncology, and conclusion.

Introduction: Haematologic Malignancies

Haematologic malignancies are clonal disorders of haemopoietic tissues.
They arise from a single transformed cell in bone marrow or peripheral lymphoid tissues.
Often, the cells of origin have pre-existing genetic alterations.
Types include various leukaemias, lymphomas, MDS and MPN.

Epidemiology: Haematologic Malignancies

Haematological malignancies account for roughly 7% of all cancers.
Incidence varies by age, sex, and geographical location.
These factors influence the disease's progression.
Charts show variation in incidence by cancer type among males and females (pie charts). Cancer types are shown, with percentage breakdowns for each gender.

Aetiology: Genetic Factors

Genetic conditions significantly increase haematological malignancy risk.
These include Down's syndrome, Bloom's syndrome, Fanconi anaemia, ataxia telangiectasia, neurofibromatosis, Klinefelter's syndrome, and Wiskott-Aldrich syndrome.
These conditions often predispose to leukaemia development.
Lymphomas (CLL and AML) also demonstrate a weak familial tendency.

Aetiology: Environmental Factors

Exposure to certain chemicals (e.g., aromatic hydrocarbons like benzene, industrial solvents) increases malignancy risk.
Exposure to radiation and specific drugs (alkylating agents like chlorambucil, melphalan, procarbazine) are also related to malignancy development.
Infective agents such as viruses (HTLV-1, EBV, HHV8, HIV) and bacteria (Helicobacter pylori) and protozoa (Malaria) are associated with haematological malignancies.

Genetics: Oncogenes

Oncogenes have the potential to induce cancer.
They develop from proto-oncogenes that are normal genes regulating critical cellular processes.
Activation or mutation of these proto-oncogenes can transform them into oncogenes (like a good cop becoming a bad cop).
Translocation and duplication are key processes in proto-oncogene mutation leading to oncogene development.
Translocation: Exchange of genetic material between non-homologous chromosomes can form a chimeric fusion gene or lead to gene overexpression, creating oncogenes.
Duplication: Leads to extra genetic activity on a duplicated chromosome part, sometimes resulting in chromosome abnormalities like trisomy.

Genetics: Tumour Suppressor Genes

Tumour suppressor genes usually regulate the cell cycle (G1 to S, S to G2).
These genes act as primary cellular control mechanisms.
A common example of a tumour suppressor gene is p53.
Loss-of-function mutations within these genes can lead to uncontrolled cell growth and cancer.
Mutations can take the form of point mutations (single base change in DNA) or deletions (loss of a chromosome part).

Diagnostic Techniques in Haemato-oncology

Karyotyping: Direct morphological analysis of chromosomes from tumour cells, often using cell cultures and colchicine induced metaphase arrest.
Polymerase Chain Reaction (PCR): Amplifies specific DNA segments (sometimes mRNA via reverse transcriptase), used for diagnosis and detecting minimal residual disease.
Flow cytometry: Uses surface-specific antigens (protein markers) to differentiate normal vs abnormal (tumour) cells based on unique profiles of expression. Uses fluorescently labelled antibodies.
Immunohistochemistry: Antibody staining of tissue sections (using fluorescent markers) to visually assess tissue characteristics (and tumour cell properties), performed by histopathologists.
Fluorescence in situ hybridization (FISH): Genetic probes (with fluorescent labels) are hybridized with patient samples to detect extra copies, gene rearrangements (translocations).
DNA microarray platform: Enables study of transcription by using known DNA probes on a solid base to assess specific sequences and expression patterns (including those of interest relating to malignant vs normal cells).
Gene Sequencing (NGS): Advanced techniques used to detect genetic mutations for malignancy; can study single or multiple genes of interest, or the whole genome.

Management of Haematological Malignancies: An Overview

An approach to treating haematologic malignancies includes multiple steps: history, physical examinations, diagnostic investigations, treatment, follow up, and prognosis stages.

Diagnostic Investigations

A battery of tests is used, including: full blood counts and differentials, peripheral blood film, bone marrow aspiration/biopsy, cytochemistry, immunophenotyping, cytogenetics, and molecular genetics.

Supportive Investigations

Important supportive investigations include clotting profiles, serum analyses (renal/liver function, electrolytes), blood glucose, virus/bacteria serology, sepsis assessments, and imaging like X-ray, ultrasound, CT and PET scan.

Treatment

Treatment: Supportive

Supportive strategies during haematological malignancy treatment include counselling, reproductive health management, nutritional support, central venous catheter insertion, intravenous fluids, blood products, antimicrobial therapy (prophylaxis), anti-uricogenic medicines, and pain relief.

Treatment: Definitive

Definitive treatments often include multi-drug chemotherapy regimens, radiation therapy, and surgical interventions (where appropriate).

Conclusion

Understanding the etiology and genetics of haematological malignancies is important for early diagnosis, treatment choices, and patient monitoring and follow up. Key diagnostic methods for malignancies include karyotyping, PCR, flow cytometry, immunohistochemistry, FISH, microarray and NGS.

Studying That Suits You

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

Description

This quiz explores haematological malignancies, focusing on their aetiology and genetics. You'll learn about common types like leukaemias and lymphomas, along with their origins and genetic background. Test your understanding of these clonal diseases and their impact on haemopoietic tissues.