Lecture 12 - Introduction to Haematological Disorders - Haematological Neoplasia Flashcards
Haematopoietic Neoplasia (Leukemia)
RBC, WBC and megakaryocyte lines can all develop into types of haematopoietic neoplasia
All these can have uncontrolled production of cells in the bone marrow
A spectrum of biological behaviour exists
- some very slowly progressive
- some very aggressive/malignant
There may be a ‘progression’ or change in the characteristics of a particular haematopoietic neoplasm throughout the course of the disease
Leukemogenesis - the process that leads to the development of hematopoietic neoplasm
Classification of Leukemia
Classification of leukemia attempts to use characteristics of the neoplastic cells to understand their biological behavior In this way, behavior and disease progression of the neoplasm can be predicted (prognosis) The characteristics used include: - morphology - immunophenotype - cytogenetic features - genetic features - clinical syndromes
Chronic Leukemia
Classified by the WHO as ‘myeloproliferative neoplasms’
Essentially in these neoplasms, the majority of the particular cell type has mostly differentiated into its mature form
- a small amount of immature forms may also be present
Chronic Myeloid Leukemia
Classified by the WHO as ‘myeloproliferative neoplasms’
No appropriate stimulus for production of cells
Many different types
Typically have increased concentration of haematopoietic cells
Composed of predominantly differentiated haematopoietic cells
Chronic Myelogenous (Myeloid) Leukemia
Chronic myelogenous leukemia is a type of chronic leukemia Often abbreviated CML FBC results (chronic phase): - WBC 12-1000 x10^9/L - median ~100 x10^9/L - > 50% mature neutrophils - < 2% blasts - concurrent eosinophilia, basophilia also common
Chronic Myelogenous Leukemia - Genetics
Can be confirmed by identifying the underlying genetic lesion
i.e. translocation between chromosomes 9 and 22 known as the Philadelphia chromosome
Or the altered gene resulting from chromosomal translocation (BCR-ABL1 fusion gene)
Chronic Lymphocytic Leukemia (CLL)
Chronic leukemia of lymphocytes
Most common leukemia in the world
Mean age of diagnosis is 72 years
CLL Diagnosis
Presence in the peripheral blood of > 5.0 x 10^9/L clonal lymphocytes
Clonality of circulating lymphocytes needs to be confirmed by flow cytometry
In FBC, leukemic lymphocytes are small, mature-appearing lymphocytes
- these cells have narrow border of cytoplasm and dense nucleus lacking nucleoli
Larger atypical lymphocytes or prolymphocytes may be seen
Disrupted/lysed (‘smudge’) cells are common
CLL Immunophenotype
CLL are of B-cell origin
CLL cells typically co-express the CD5 antigen and B cell surface antigens CD19, 20 and 23
The levels of surface immunoglobulin, CD20 and CD79b are low compared with those found on normal B cells
Acute Leukemia
Known as acute myeloid leukemia or precursor lymphoid neoplasms
Essentially contain neoplastic cells that have not differentiated (matured) from the blast form into their ultimate form
Proportion of blasts varies greatly
Greater than 20% blast cells is indicative of acute leukemia
What identifies a blast cell?
Poorly differentiated precursor haematopoietic cell
High nuclear:cytoplasmic ratio
Course chromatin
Nucleolus evident
Acute Leukemia Clinical Presentations
Usually dysplasia of bone marrow Anaemia => pallor and fatigue Thrombocytopenia => bruising and bleeding Neutropenia => fever and infections WBC typically between 5 - 30 x10^9/L (can be as high as 200) Further tests: - immunophenotype - karyotype - molecular biology
Clinical Haematological Methods to Identify Cell Origin/Lineage
Cytochemistry - used to determine cell lineage - e.g. myeloproliferative detects cells of myeloid origin Immunophenotype - flow cytometry - used to determine cell lineage - e.g. CD markers Cytogenetics - karyotype; FISH - used to determine chromosomal abnormalities Molecular Biology - used to detect specified genetic 'lesions'
