Leukemia: Types, Causes and Symptoms

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What is Leukemia?

Leukemia is the neoplastic proliferation of hematopoietic precursor cells. Normal WBCs in peripheral circulation are about 4000-11000mcL. When WBCs is more than 11000 mil, is called Leukocytosis. When WBCs are less than 4000 mcL, is called Leukopenia.

Types of proliferation of White Blood Cells (WBCs)

There are two types of proliferation of WBCs: 1. Reactive proliferation. 2. Neoplastic proliferation

Defining Reactive Proliferation of White Blood Cells

When WBCs increase in peripheral circulation in response to some trauma, infection and inflammation is called reactive proliferation.

a) What is Simple Leukocytosis? (Mild-moderate leukocytosis)

This is a type of reactive proliferation in which mild to moderate leukocytosis occurs. In this type, we can find following subtypes of WBCs out of proportion. For example;
  • Pyogenic infection leads to Neutrophilic leukocytosis or Neutrophilia.
  • Parasitic infection leads to Eosinophilic leukocytosis or Eosinophilia.
  • Allergy, drug reactions or specific neoplasias produce Basophilic leukocytosis.
  • Tuberculosis produces Lymphocytosis.
  • Chronic inflammation and infections produce Monocytosis

b) What is Leukemoid Reaction? How Severe Leukocytosis Occurs (30000-50000 mcL)

This is a type of reactive proliferation in which severe leukocytosis occurs. Normally, haemopoiesis takes place in the bone marrow in adults and then WBCs go to the circulation. Some WBCs produced in the bone marrow remain in the bone marrow; this is called the bone marrow storage pool of WBCs. Some of the peripheral WBCs stick with endothelial cells; this is called the marginated pool of WBCs. When there is severe or prolonged stress (inflammation, infection, trauma, surgery etc.) In our biological system, the following changes occur which eventually lead to increase WBCs in the circulation:
  1. Bone marrow storage pool of WBCs can be mobilized
  2. Marginated pool of WBCs
  3. Over stimulation of production house, i.e., Bone marrow
Leukemoid reaction can be differentiated from CML, for example, there is high leukocyte alkaline phosphatase score (LAP score) in Leukemoid reaction whereas in CML there is a low LAP score. Leukemoid reaction can also be differentiated from AML, for example, there are abundant blast cells present in peripheral circulation as well as in bone marrow (>20%) in AML whereas in Leukemoid reaction, blast cells in peripheral circulation or bone marrow almost never go more than 20%.

Neoplasia – Definition, Types & Examples

Leukemia

Leukemia is the neoplastic proliferation of hematopoietic precursor cells, which diffusely involves the bone marrow and have a tendency to go to the circulation in a diffuse pattern, this type of behavior shown by such malignant cells is called leukemia. The clinical presentation of leukemia is associated with bone marrow failure due to the diffuse spread of leukemic cells.

 Lymphoma

Lymphoma is also the neoplastic proliferation of hematopoietic precursor cells, but these malignant cells do not spread diffusely in the bone marrow rather they make a discrete and well defined mass in the bone marrow or any lymphoid tissue (thymus, lymph nodes, spleen and liver etc.). They may go to the circulation in very small amount to metastasize and infiltrate into the tissues (intestine, brain etc.). This type is called lymphoma.

Major Difference between Leukemia and Lymphoma

The real difference between leukemia and lymphoma depends upon the distribution of the malignant hematopoietic precursorc cells and how they clinically present in the body. That’s why lymphoid neoplasias can be leukemic or lymphomatous. Sometimes the disease can start as leukemia and may have lymphoma mass or sometime disease can start as lymphoma and it may end up into leukemic phase. When a patient comes to the doctor, actually we should see the distribution of the malignant hematopoietic precursor cells in the body. In an example of chronic lymphocytic leukemia/ small cell lymphoma (CLL/SCL), both have same malignant cells, same cytogenetic abnormalities or may be similar kind of treatment even, but they have different distribution patterns of the malignant hematopoietic precursorc cells.

Neoplastic proliferation of White Blood Cells (WBCs)

It is usually divided into three categories:
  1. Lymphoid neoplasms.
  2. Myeloid neoplasms.
  3. Histiocytic neoplasms.

1. Definition of Lymphoid neoplasms (WHO classification)

Lymphoblasts are central, immature, undifferentiated and large cells and rapidly proliferate whereas lymphocytes are peripheral, mature, differentiated and small cells (e.g., B-cells, T-cells and NK). In the case of leukemia, lymphoblast cells undergo neoplastic proliferation (uncontrolled proliferation) but cannot become mature lymphocytes (B-cells, T-cells and NK). They keep on proliferating and eventually replace the normal lymphoblasts and start consuming the growth factors and nutrition, as a result, normal lymphoblast count gradually reduces. This may lead to excess of neoplastic lymphoblasts and deficiency of normal cells in the body, leading to different clinical problems in the body. In acute leukemias or aggressive lymphomas, maturation arrest occurs early (near the lymphoblast cells), proliferation continues and patient will develop clinical problems within weeks or months. In chronic leukemias or less aggressive lymphomas, maturation arrest occurs late (near the mature cells), less proliferation occurs and the patient will gradually develop clinical problems within months or years. According to classification:
  1. Precursor B-cells neoplasia (Pre B-ALL)
  2. Peripheral B-cells neoplasia e.g., CLL/SCL, hairy cell leukemias, Burkitt lymphoma
  3. Precursor T-cells neoplasia (Pre T-ALL) or Precursor NK-cells neoplasia (Pre NK-ALL)
  4. Peripheral T-cells neoplasia or Peripheral NK-cells neoplasia.
  5. Hodgkin lymphoma.

 Hodgkin lymphoma

These lymphoma masses, under the microscope have a special type of giant cells called Reed Sternberg cells having typically bilobed nucleus (Owl’s eye appearance).  Hodgkin lymphoma has very good prognosis.
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