Question

1. 1. How do critical windows of exposure and different sub-types of leukemia make associates between causative substances and the occurrence of leukemia difficult to detect?
2. 2. What is the two-hit model? How is it related to the term gene-environment interactions?

Answer 1

LEUKEMIA

It is unregulated proliferation or accumulation of white blood cells in the bone marrow. Immature proliferation of white blood cells.

Classification into two types acute or chronic. It depends upon the development of rate of symptoms.

Classification depends upon predominant cell type ;

Lymphocytic leukemia - Lymphocytes are predominately.

Myelogenous leukemia - It is characterized by proliferation of myeloid cells including granulocytes,monocytes, platelets, and occasionally red blood cells.

Acute lymphocytic leukemia - It is due to malignant proliferation of lymphoblast.

Age of onset - before 15 years of age young children males affected>females

Acute myelogenous leukemia - affects the hematopoietic stem cells that differentiates into all myeloid cells.

Age of onset- 15&39 years

Chronic lymphocytic leukemia - Involves more mature cells that acute leukemia. Onset of age is after 50 years.

Chronic myelogenous leukemia - Proliferation of myeloid cell lines and more mature cells are present than acute. Age of onset after 50 years.

Causes

Main causes are,

Exposure to ionizing radiation

Exposure to chemical and toxins

Hereditary

Genetic disorders eg; down syndrome

Signs and symptoms

- Anorexia

- Fatigue

- weakness

- weight loss

- Anemia

- Bleeding

- Elevated temperature

- Palpitations

- Tachycardia

- Orthostatic hypotension

- Headache

- Pallor

- Dyspnea on exertion

- Bone pain and joint pain

- Thrombocytopenia

- Granulocytopenia

- Lymphadenopathy

- Spleenomegaly

- In chronic cases early s/s are ,. Skin or respiratory infections and mild Spleenomegaly

Diagnostic evaluation

CBC and blood smear; increased WBC count 1000-100000/mm3 decreased RBC count decreased platelet count

Bone marrow aspiration and biopsy - to determine the type of leukemia, chromosomal abnormality

Lymph node biopsy that is to detect metastasis

MEDICAL MANAGEMENT

- Chemotherapy

- Leukapherasis ( exchanged transfusion)

- Radiation to CNS

- Bone marrow transplantation

  

Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings shown that the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia initiating target cell. This driving of cancer by a malignant epigenetic stem cell rewiring is, however,not exclusive of the hematopoietic system, but rather represent a common tumoral mechanism that is also at work in epithelial tumors. Tumoral epigenetic reprogramming is therefore a new type of interaction between genes and their target cells,in which the action of the oncogene modifies the epigenome to prime leukemia development by establishing a new pathological tumoral cellular identity. This reprogramming may remain latent until it is triggered by either endogenous or environmental stimuli. The pathogenesis of leukemia is well characterized in the two hit hypothesis of acute myeloid leukemia. This model describes at least two genetic alterations required for leukemogenesis. Class 2 mutations cause defects in myeloid cell differentiation. These occur early and result in maturation arrest.