Pathological Conditions Related to Leukocytes

What is Leukemia

Cancers that originate in the bone marrow

• Uncontrolled proliferation of abnormal white blood cells

What are acute leukemias?

Fast-growing undifferentiated cells; blasts

What are chronic leukemias?

Progress more slowly & involves more mature WBCs

Differentiate between acute and chronic leukemias

Acute:

• Fast-growing undifferentiated cells; blasts

Chronic:

• Progresses slowly

• Involves more mature WBCs

What are Lymphocytic/Lymphoblastic leukemias?

Involves uncontrolled proliferation of abnormal lymphoid progenitors cells → lymphocytes (T cells, B cells, NK cells)

What are Myelocytic/Myeloid leukemias?

Involve uncontrolled proliferation of abnormal myeloid progenitor cells (granulocytes, monocytes, RBCs, Plts)

What are the main types of leukemias (4):

• Acute lymphocytic leukemias (ALL)

• Acute myeloid leukemia (AML)

• Chronic lymphocytic leukemia (CLL)

• Chronic myeloid leukemia (CML)

What initially causes Acute Lymphocytic Leukemia (ALL)?

• Genetic & environmental factors

Is Acute Lymphocytic Leukemia more common in children or adults? Who has a more favourable prognosis?

Children; favourable prognosis

• Adults have poor prognosis

Describe how Acute Lymphocytic Leukemia progresses; pathogenesis

Immature lymphoblasts in the bone marrow undergo malignant transformation → loss ability of normal lymphocyte differentiation

What are the structural alterations of Acute Lymphocytic Leukemia

• Bone marrow becomes backed with immature lymphoblasts

• Chromosomal abnormalities → Philadelphia chromosome

What is the clinical significance of ALL (Acute Lymphocytic Leukemia)

• Anemia (fatigue)

• Thrombocytopenia (bleeding)

• Neutropenia (Infection)

• Fever, bone pain, swollen lymph nodes

What is CML

Chronic Myeloid Leukemia

How does Chronic Myeloid Leukemia occur?

Translocation of chromosomes 9 & 22 → formation of Philadelphia chromosome → BCR-ABL fusion gene → tyrosine kinase abnormally active → uncontrolled cell proliferation

What is the name of the chromosomal abnormality that occurs in ALL and CML?

Philadelphia chromosome

What is the Philadelphia chromosome?

It is the creation of a fusion gene (BCR-ABL) due to a translocation between chromosome 22 & 9; causes an abnormally active tyrosine kinase; uncontrolled cell proliferation

What is the chronic phase of CML?

• Asymptomatic, mild symptoms

  • Fatigue

  • Weight loss

  • Splenomegaly

What is the accelerated phase of CML?

Gradually worse symptoms:

• Increase WBCs

• Treatment resistance

What is Blast crisis phase of CML?

CML transforms into an aggressive acute leukemia (ALL, AML) → bone marrow failure

What is lymphoma?

Cancers that arise from lymphocytes

Where do lymphomas develop

In the lymphatic system

What is Hodgkin’s lymphoma

Cancer that arises from lymphocytes

• Presence of Reed-Sternberg cells (large abnormal lymphocytes)

• Starts in a single lymph node or chain of nodes and spreads

• Favourable prognosis

What is Non-Hodgkin’s lymphoma?

Cancer that arises from lymphocytes (B/T)

• Diverse lymphoid malignancies; does not involve Reed-Sternberg cells

• Can develop in ANY part of the body and spreed; more diffuse than Hodgkin’s

What is an example of a indolent (slow-growing) lymphoma?

Follicular lymphoma

What is an example of highly aggressive types of lymphomas?

• diffuse large B-cell lymphoma (DLBCL)

• Burkitt lymphoma

Why/How is Non-Hodgkin’s Lymphoma caused?

• t(14;18) chromosomal translocation → overexpression of BCL2 gene (anti-apoptotic gene) → cancer

• Immunodeficiency & environmental factors

• Chronic infections (EBV, H. Pylori, HTLV)

Describe the pathogenesis of Non-Hodgkin’s Lymphoma, how does it progress?

• malignant transformation of B or T lymphocytes at various stages of differentiation (commonly B cells)

  • Accumulates and forms tumors

• Affects Primary lymphoid tissues (BM), secondary lymphoid tissues (lymph nodes, spleen, etc.)

What are the structural alterations of Non-Hodgkin’s Lymphoma?

• Lymph Node enlargement

• Nodular patterns

  • Diffuse

  • Nodular

• Bone marrow involvement → pancytopenia

• Extranodal involvement (affect external organs)

Describe diffuse Nodular patterns of NHL

Dispersed cells throughout the lymph node

Describe ‘Nodular’ nodular patterns of NHL

Clumped cells forming nodules

What is the clinical significance of NHL?

• Painless lymphadenopathy (enlarged lymph nodes)

• B symptoms → fever, night sweats, weight loss

• Extranodal symptoms