sq
sq

Leukemia

HSBTE DMLT hematology IVth Semester UNIT III Leukemia: Definition of leukemias. (FAB) Classifications. Laboratory diagnosis of various leukemias.

HAEMATOLOGY

Dr Pramila Singh

3/24/20243 min read

HSBTE. DMLT. Hematology. IVth-Semester Leukemia: Definition of leukemia. (FAB) Classifications. Laboratory diagnosis of various leukemia. UNIT III

Definition of leukemias.

"Leukemias are a group of malignant disorders characterized by the uncontrolled growth of abnormal white blood cells (leukocytes) in the bone marrow and blood".

This results in an overproduction of immature or dysfunctional white blood cells. This impairs the normal functioning of the bone marrow. It decreases the immunity of the human body. These abnormal cells are referred to as leukemia cells.

Leukemias are classified into various subtypes based on the specific type of white blood cell affected (lymphoid or myeloid) and the degree of cell maturity. Leukemias can be categorized into acute leukemia and chronic leukemia.

Leukemias are classified into different subtypes based on the specific type of white blood cell affected (lymphoid or myeloid) and the degree of cell maturity. Leukemias can be categorized into acute and chronic forms.

Acute Leukemia Etiology:

The exact reason is unknown. However, increased incidence of the following develops acute leukemia:

  • i. Increased radiation exposure or benzene exposure,

  • ii. Prolong use of chloramphenicol, phenylbutazone, or arsenic

  • iii. Prolong cytotoxic therapy.

  • iv. Congenital factors and immunologic deficiency.

Various Terms Used in Leukemia

A. Leukemias types depending upon the duration of the disease.

  1. Acute Leukemia: Leukemia duration from several days to six months.

  2. Subacute Leukemia: Leukemia duration is two months to six months

  3. Chronic Leukemia: Leukemia duration of one to two years or more.

B. Leukemias types depend upon the number of cells present in the peripheral blood

  1. Leukemic Leukemia: Peripheral blood containing more than 15,000/cu mm of WBCs.

  2. Subleukemic Leukemia: Peripheral blood containing less than 15,000/cu mm of WBCs. Presence of immature (Abnormal) WBCs in the peripheral blood

  3. Aleukemic Leukemia: Peripheral blood containing less than 15,000/cu mm of WBCs. No immature (Abnormal) WBCs present in the peripheral blood smear.

C. Leukemias types depend upon the White blood cells involved

  1. Granulocytic leukemia (Myelogenous leukemia): Leukemia due to abnormal neutrophils and their precursors.

  2. Eosinophilic leukemia: Leukemia due to abnormal eosinophil and their precursors.

  3. Basophilic leukemia: Leukemia due to abnormal basophils and their precursors.

  4. Lymphocytic leukemia: Leukemia due to abnormal lymphocytes and their precursors.

  5. Monocytic leukemia: Leukemia due to abnormal monocytes and their precursors.

  6. Myelomonocytic leukemia: Leukemia is caused by two or more abnormal cells and their precursors. Normally megakaryocytes and red blood cells precursors along with monocytic and granulocytic cells.

  7. Erythroleukemia: Leukemia due to abnormal erythrocytes (red blood cells) and granulocytic precursors.

  8. Lymphosarcoma cells leukemia: Leukemia due to lymphosarcoma.

  9. Stem cell leukemia: Leukemia due to abnormal primitive blast cells.

  10. Erythremia myelosis: Leukemia due to abnormal red blood cell precursors.

Acute myelogenous leukemia (AML): Leukemia duration not more than six months and due to abnormal myeloid or hematopoietic stem cells is called AML.

Acute lymphoblastic leukemia (ALL): Acute lymphoblastic leukemia (ALL) is also known as acute lymphocytic leukemia. Leukemia duration is more than one year and due to abnormal lymphoblasts is called ALL.

ALL is the most common type of leukemia in children, but it can also occur in adults. The exact cause of ALL is often unknown. However, genetic factors, environmental exposures, and medical conditions may increase the risk.

Chronic Lymphocytic leukemia (CLL): Chronic lymphocytic leukemia (CLL) is a type of cancer that affects a specific type of white blood cells (lymphocytes). Leukemia duration is more than one year and due to abnormal lymphocytes and their precursors is called CLL.

The exact cause of CLL is not fully understood. However, age (CLL is more common in older adults), family history of CLL or other lymphoproliferative disorders, and exposure to certain environmental factors such as certain chemicals or radiation increase the risk. 

(FAB) Classifications

The French-American-British (FAB) classification system was widely used for classifying various types of acute leukemias. The FAB classification aimed to classify acute leukemias based on the morphology (appearance and structure) of the leukemia cells (leukocytes). It is applied to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The FAB classifications have been replaced by more advanced molecular and cytogenetic classifications. However, it still provides historical context and is occasionally referenced in medical literature. The following are the main categories under the FAB classification.

Myeloblastic cells: Myeloblastic cells are the early-stage cells in developing granulocytes in bone marrow. Myeloblasts differentiate into promyelocytes. Promyelocytes mature into myelocytes, metamyelocytes, and finally into the mature granulocytes: neutrophils, eosinophils, and basophils.

Myeloblastic cells can be identified microscopically in bone marrow samples. They are significant in the diagnosis and classification of various blood disorders, including acute myeloid leukemia (AML). In AML an abnormal proliferation of myeloblasts occurs.

Myeloblastic cells are part of the myeloid cell lineage. myeloid cell lineage also includes erythrocytes (red blood cells) and platelets (thrombocytes).

A. Acute Myeloid Leukemia (AML):

1. M0: Undifferentiated Acute Myeloblastic Leukemia: Characterized by undifferentiated myeloblasts or minimally differentiated myeloblasts.

  • Cell Type: Primitive cells.

  • Characteristics: Undifferentiated or minimally differentiated myeloblasts.

2. M1: Acute Myeloblastic Leukemia Without Maturation: Myeloblasts show minimal maturation. Lack the development into more mature myeloid cells.

  • Cell Type: Myeloblasts

  • Characteristics: Non-granular myeloblasts. Contains one or more distinct nuclei.

3. M2: Acute Myeloblastic Leukemia With Maturation: Myeloblasts show partial maturation. Presence of more mature forms of myeloid cells, such as promyelocytes and myelocytes.

  • Cell Type: Myeloblasts and promyelocytes

  • Characteristics: Maturation beyond promyelocytes state. Cells contain Auer rods.

4. M3: Acute Promyelocytic Leukemia (APL): Characterized by the presence of promyelocytes. Associated with a specific genetic abnormality involving the retinoic acid receptor (RARα).

  • Cell Type: Hypergranular promyelocytes. 

  • Characteristics: Most of the cells are promyelocytes. Characteristic heavy granulation pattern

5. M4: Acute Myelomonocytic Leukemia: Presence of both myeloblasts and monoblasts. Monoblasts can develop into monocytes.

  • Cell Type: Monocytoid cells. 

  • Characteristics: Immature and mature cells of both myeloid and monocytic lineage.

6. M5: Acute Monocytic Leukemia: Predominance of monoblasts and promonocytes. Involves infiltration of tissues by monocytic cells.

  • Cell Type:

    • M5(a): Monoblasts. 

      M5(b): Monoblasts, Pro-monocytes and Monocytes.

  • Characteristics:

    • M5(a): Poorly differentiated monoblastic

    • M5(b): Differentiated  Monoblasts, Pro-monocytes and Monocytes

7. M6: Acute Erythroid Leukemia: Characterized by a predominance of erythroid precursors. Involves abnormal proliferation of erythroid cells.

  • Cell Type: Erythroblasts

  • Characteristics: Erythroblasts with multiple lobes of the nucleus, multiple nuclei, nuclear fragments, and giant forms megaloblastic features

8. M7: Acute Megakaryoblastic Leukemia: Predominance of megakaryoblasts. Involves abnormal proliferation of megakaryocytic cells.

  • Cell Type: Megakaryocytes. 

  • Characteristics: Imature megakaryocytes with abnormal platelets.

Acute Lymphoblastic Leukemia (ALL)

1. L1: Acute Lymphoblastic Leukemia: Small, uniform lymphoblasts.

  • Cell Type: Microlymphoblasts

  • Characteristics: Small lymphoblasts, less cytoplasm, regular round nuclei, nuclei often not present

2. L2: Acute Lymphoblastic Leukemia: Large, more variable lymphoblasts. May have more prominent cytoplasm and nucleoli.

  • Cell Type: Large undifferentiated lymphoblasts

  • Characteristics: Larger lymphoblasts, irregular or cleft nuclei present

3. L3: Acute Lymphoblastic Leukemia (Burkitt’s): Resembles Burkitt's lymphoma. Characterized by high mitotic activity and starry sky appearance.

  • Cell Type: Burkitt type

  • Characteristics: Large blast cells with oval to round nuclei. basophilic cytoplasm. The majority of cells are undifferentiated type. 

The FAB classification system has limitations. It is unable to explain the molecular and genetic characteristics of leukemias. More modern classifications, such as the World Health Organization (WHO) classification, have become the standard for diagnosing and categorizing leukemias, which includes both morphological and genetic information. But it is not discussed here because not in the syllabus of HSBTE.