Essay 44-Leukaemia Definintion,Etiology,Pathogeneis and types

Definition

a group of malignant neoplasms originating from hematopoietic stem cells. It is primarily characterized by:

• Diffuse replacement of the bone marrow by unregulated, proliferating, immature neoplastic (blast) cells.

• Disruption of normal hematopoiesis, leading to anemia, thrombocytopenia, and neutropenia.

hemopoietic stem cells

Hemopoietic stem cells are the origin of all blood cells

HSCs —> immature blast cell —> mature specialised cell

how do the malignant neoplasms form?

the HSCs —> immature blast cell that can’t mature (mutation)

• called leukemic blast cells

stops the process of becoming specialised

• Also has another mutation, uncontrolled cell division

• they replicate lots

the HSCs should make more healthy Immature B/Cs

However, not enough space, nutrients and GFs in the bone marrow

• The uncontrolled ones are taking them all

Bone marrow gets taken over by the leukemic blast cells

• ⇓ in RBCs, platelets and WBCs

Etiology of leukemia

• Environmental

• genetic abnormalities

• therapy-related

• genetic predisposition

Environmental and chemical exposures:

Ionising radiation (e.g. atomic bomb survivors, radiation therapy).

• causes DNA damage in HSCs in the bone marrow

• RESULTS IN :

  • Double-stranded DNA to breakpoint mutations

    • activates oncogenes

    • or inactivates tumour suppressor genes

    • = malignant transformation

Exposure to benzene, certain drugs, industrial toxins, chemicals, and gases.

Genetic abnormalities:

• Chromosomal translocations and mutations such as:

  • Philadelphia chromosome (t(9;22)), commonly associated with Chronic Myelogenous Leukaemia (CML).

• Gene mutations that disrupt normal cell cycle control and differentiation.

Therapy-related leukaemia:

May occur as a secondary malignancy following chemotherapy or radiotherapy, especially in Hodgkin's lymphoma.

Genetic predisposition:

Increased incidence seen in congenital disorders such as:

• Down syndrome

• Fanconi anemia

• Bloom syndrome