HEMATOLOGICAL MALIGNANCIES Flashcards
INTRODUCTION
Haematologic malignancies are clonal diseases that involve haemopoietic tissues
- They derive from a single cell in the bone marrow or peripheral lymphoid tissues
- They include the leukaemias, lymphomas, Myelodysplastic syndrome (MDS) and Myeloproliferative neoplasms (MPN).
•Genetic diseases that greatly increase the incidence of haematologic malignancies include: •Down’s syndrome •Bloom’s syndrome •Fanconi’s anaemia •Ataxia telangiectasia •Neurofibromatosis •Klinefelter’s syndrome •Wiskott-Aldrich syndrome These mostly predispose to Leukaemias
Environmental Factors
- Exposure to chemicals e.g. aromatic hydrocarbons (benzene), industrial solvents, etc.
- Exposure to radiation
- Drugs, especially alkylating agents (chlorambucil, melphalan, procarbazine)
•Infective agents
All of the above cause varying degrees of cell injury and damage, with subsequent proliferation of aberrant, abnormal cells
Viruses
•Human T-lymphotropic virus type 1 (HTLV-1)
•Epstein Barr Virus (EBV)- ENDEMIC BURKITTS LYMPHOMA
•Human Herpes Virus 8 (HHV 8)- KAPOSI SARCOMA
•HIV – Lymphoma at unusual sites
Bacteria
•Helicobacter pylori- MALT LYMPHOMA
Protozoa
Malaria- predisposes to endemic Burkitts lymphoma
GENETICS
When Genetic mutations accumulate in cellular genes, malignant transformations results
2 group of genes involves (Oncogenes and Tumor supressor genes)
ONCOGENES
These are genes with the potential to cause cancer
•They initially existed as proto-oncogenes
•Proto-oncogenes are normal genes involved in a variety of important cellular processes such as (signal transduction )from the exterior to the nucleus, gene activation, etc.
•When the activity of these proto-oncogenes increase or when they acquire new functions (gain-of-function mutation), they transform to become oncogenes
•More like a good cop becoming a bad cop. And they become bad by 2 processes (Translocation and Duplication)
TRANSLOCATION
A chromosomal abnormality resulting from exchange of parts between Non homologous chromosomes (and in the process genetic material is exchanged between the 2 chromosomes)
Occurs In CML and AML
Results in
A. Formation of Chimeric Fusion Gene
B. Over expression of normal cellular gene
DUPLICATION
Chromosomal duplication leads to extra genetic activity on the part of the chromosome duplicated
An example is seen in Trisomy 12 in CLL
TUMOR SUPPRESSOR GENES
These are normal genes that serve as control mechanisms in regulating cell cycle
Most common example is P53 gene
Unlike Oncogenes which acquires Gain of function, Tumor suppressor genes by acquiring loss of function mutation end up causing cancer genes
Happens by 2 processes just like Oncogenes
1. Point Mutations: Genetic Mutation whereby a single Nucleotide base is changed, inserted or deleted from a sequence of DNA or RNA
- Deletions: in deletion part of the chromosome is deleted, may involve the long arm or the short arm e.g 5q deletion of myelodysplastic syndrome, 13q14 deletion of CLL
Could also involve entire chromosomes
Deletions of multiple chromosomes is termed Hypodiploidy seen in ALL (Acute Lymphoblastic Leukemia)
DIAGNOSTIC TECHNIQUES IN HEMATO ONCOLOGY
- Karyotyping
- Polymerase Chain Reaction
- Flow cytometry
- Immunohistochemistry
- Fluorescent in situ hybridization analysis
- Gene sequencing
Overview of management
HISTORY •PHYSICAL EXAMINATION •INVESTIGATIONS •TREATMENT •FOLLOW UP •PROGNOSIS
SUPPORTIVE INVESTIGATIONS Clotting profile •Serum U/E, Cr •Blood sugar •Liver function tests •Uric acid, Ca2+, Phosphate •Background viral serology (medico-legal implications) •Sepsis work up
TREATMENT : SUPPORTIVE
Counselling •Reproductive issues •Nutritional support •Determine baseline performance status of patient •Insertion of a central venous catheter •Intravenous fluid administration •Blood and blood product support •Anti-infective agents (prophylaxis) •Anti-uric acid agents •Analgesics
TREATMENT : DEFINITIVE
Combination Cytotoxic Therapy
Radiation
•Surgery – where applicable
