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Etiology, genetics and classification of hematological malignancies. By/ Mr. Waqqas Elaas ; M.Sc ; MLT. Objectives . At the end of this lecture, the student should understand: Definitions of some terminologies regarding Hematologic malignancies.
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At the end of this lecture, the student should understand:
Carcinogenesis is caused by this mutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (cancer).
Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they compress vital structures or are physiologically active, for instance, producing a hormone.
Cancer is a genetic disease: In order for cells to start dividing uncontrollably, genes that regulate cell growth must be damaged.
a. Chemicals : Chronic exposure to benzene may cause bone marrow hypoplasia, dysplasia and chromosome abnormalities and is an unusual cause of myelodysplasia or AML. Other industrial solvents and chemicals less commonly cause leukaemia.
b. Drugs : The alkylating agents (e.g. chlorambucil) predispose to AML, especially if combined with radiotherapy or if used to treat patients with lymphocytic or plasmacytic disorders.
c. Radiation : Radiation, especially to the marrow, is leukemogenic. This is illustrated by an increased incidence of all types of leukemia (except CLL) in survivors of the atom bomb explosions in Japan.
Appr. : HHV-8, human herpes virus 8; HIV, human immlmodeficiency virus; HTLV-I,
human: T-lymphotropic virus type 1; MALT, mucosa-associated lymphoid tissue;
PTLD, post-transplant lymphoproliferative disease.
oncogenes and tumour-suppressor genes.
Duplication or amplification:In chromosomal duplication (e.g. trisomy 12 in CLL) or gene amplification, gains are common in chromosomes 8, 12, 19, 21 and y. Gene amplification is not a common feature in haemopoietic malignancy.
G-banded karyogram with the translocation (8;21)(q22;q22) as the only anomaly. This change is seen exclusively in (AML/M2)
*Involves the use of fluorescent-labeled genetic probes which hybridize to specific parts of the genome.
* a sensitive technique that can detect extra copies of genetic materials in both METAPHASE and INTER-PHASE (non-dividing) cells (e.g. trisomy 8 in some CML) or by using two different probes reveal chromosomal translocations, for example, t(9;22) in CML or reduced chromosome numbers or segments (e.g. monosomy7 or 5 in myelodysplasia).
*Antibodies labeled with different fluorochromes recognize the pattern and intensity of expression of different antigens on the surface of normal and leukemic cells.
* A rapid technique.
CD : Cluster of Differentiation
*Is used to amplify specific region of DNA (target), can be performed on blood or bone marrow for a number of specific translocations such as t(9;22) and t(15;17). It can also be used to detect clonal cells of B- or T-cells line.
*Sensitive method (why?):
(detects one abnormal cell in 10⁵- 10⁶ n.c)
(a) when these techniques are not available, and
(b) in making a provisional morphological diagnosis while awaiting the results of further tests (immunophenotypingandcytogenetics).
The World Health Organization (WHO) Classification includes tumors of lymphoid, myeloid, histiocytic, and dendritic cell lineages.• Each disease is defined as a distinct entity based on morphological, clinical, and biological features but the cell of origin is the starting point of disease definition.• Some lymphomas and leukemias can be identified by routine morphological approaches. However, for many diseases, knowledge of the immunophenotype and molecular genetics/cytogeneticsplays an important role in differential diagnosis.
-Precursor Lymphoid Neoplasms
-Mature B-Cell Neoplasms
-Mature T-Cell and NK-Cell Neoplasms
-Histiocytic and Dendritic Cell Neoplasms
-Post-Transplant Lymphoproliferative Disorders