Chronic lymphocytic leukemia pathophysiology

Chronic lymphocytic leukemia Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Chronic lymphocytic leukemia from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
Staging
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Chronic lymphocytic leukemia pathophysiology On the Web
Most recent articles
cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Chronic lymphocytic leukemia pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Chronic lymphocytic leukemia pathophysiology
CDC on Chronic lymphocytic leukemia pathophysiology
Chronic lymphocytic leukemia pathophysiology in the news
Blogs on Chronic lymphocytic leukemia pathophysiology
Directions to Hospitals Treating Chronic lymphocytic leukemia
Risk calculators and risk factors for Chronic lymphocytic leukemia pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

Overview

Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleoli, and presence of smudge cells.

Pathogenesis

• Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production.
• Malignant lymphocytic cells infiltrate hematopoietic sites such as the bone marrow where they interfere with the production of red blood cells.
• Chronic lymphocytic leukemia may also infiltrate the lymph nodes, spleen, and liver.
• Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.
• Warm autoimmune hemolytic anemia may develop due to the production of IgA and IgG autoantibodies among certain cases of chronic lymphocytic anemia.
• Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.
• Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing large B cell lymphoma.

Genetics

• Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells.
• Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:

• Chromosome 13 long arm deletion (most common genetic mutation)
• Chromosome 17 short arm deletion
• Chromosome 11 long arm deletion
• Trisomy 12

• Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:

• NOTCH1 gene located on chromosome 9
• MYD88 gene located on chromosome 3
• TP53 gene located on chromosome 7
• ATM gene located on chromosome 11
• SF3B1 gene located on chromosome 2
• FBXW7 gene located on chromosome 4
• CHD2 gene located on chromosome 15

• Production of cytokines, angiogenic factors, and chemokines by the surrounding macrophages and T cells provide important stimuli for the malignant B cells proliferation in chronic lymphocytic leukemia.

Microscopic Pathology

• On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:

• Small lymphoid cells
• Thin cytoplasmic border
• Dense nucleus
• Lack of nucleoli
• Clumped chromatin aggregates
• Smudge cells
• Gumprecht nuclear shadows

• On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:

• CD5 +ve
• CD19 +ve
• CD20 +ve
• CD23 +ve/-ve
• CD43 +ve
• Cyclin D1 -ve
• CD38 -ve/+ve

• Shown below is a series of microscopic images seen in multiple myeloma:

• 

  Chronic lymphocytic leukemia demonstrated on low magnification

• 

  Chronic lymphocytic leukemia demonstrated on intermediate magnification

• 

  Chronic lymphocytic leukemia demonstrated on high magnification

• 

  Chronic lymphocytic leukemia demonstrated on very high magnification

References

Template:WikiDoc Sources