THE LEUKEMIAS
JOACHIM B. DOMOSIE
Neutrophils Bacterial infection, cancer, hemorrhage, trauma, administration of steroids, intoxication
Typhoid, virus infection, granulopenia, aplastic anemia, AIDS
Lymphocytes Virus infection, pertussis, tuberculosis, lymphocytic leukemia
Immunodeficiency disease, Hodgkin’s disease, drugs (chemotherapy), radiation damage
Monocytes Bacterial infection, malaria, monocytic leukemia, Hodgkin’s disease, Toxoplasma thyroid infection
Administration of steroids or Antipurine
Eosinophils Allergy, tumour, autoimmune disease, Hodgkin’s disease
Stress, Cushing’s disease
Basophils Chronic myelogenous leukemia, urticaria, asthma
Stress, hyperthyroidism
Atypical lymphocytes
Appear transiently in viral infection or allergic conditions
Cancer
• Cancer is a term to describe a plethora of malignancies characterized by
abnormal cellular proliferation, growth and differentiation with potential to
invasively metastasis from primary sites of origin in to secondary anatomic
niches.
• An estimated 18.1 million new cases of cancer and 9.6 million cancer associated
mortality occurred in 2018 (Globocan 2018)
• Cancer-related mortality would displace infectious diseases associated mortality
as the leading rank of mortality in the 21st century.
• Cancer is a multi-step genomic mutations
• Alter normal cellular control of molecular networks responsible for cell proliferation,
differentiation and apoptosis
• Induce a state of functional autonomy of the clonally transformed cells
• It creates a supportive microenvironment
• Mutations affect oncogenes, tumor suppressor and DNA damage repair genes
• Germline mutations - genetic inheritance , somatic mutations
Solid tumors Liquid tumors
•Cancerous growths forming lumps or masses in specific organs •Also called blood cancers, they involve cancer cells
or tissues. e.g breast, prostate, lung, colon cancer that circulate in blood, bone marrow, or lymphatic
•Sarcomas: cancers arising from connective system. eg.
or supporting tissues (bone, muscle) •Leukaemias
•Carcinomas: cancers arising from the •Lymphomas
body‘s glandular and epithelial cells •Myeloma
Hallmarks of cancer
Definition of Leukaemia
• Leukemias are malignant diseases characterized by
unregulated proliferation of WBC with a spill-over into
peripheral blood circulation.
• It may involve any of the cell lines or a stem cell common to
several cell lines.
• Leukaemias are classified into 2 major groups
• Chronic - onset is insidious, usually less aggressive,
and involves more mature cells.
• Acute - onset is usually rapid, the disease is very
aggressive, and the cells involved are usually
poorly differentiated with many blasts.
Types
• Both acute and chronic leukaemias are further classified
according to the prominent cell line(s) involved in the
expansion:
• If the prominent cell line is of the myeloid
lineage it is a myelocytic leukaemia (sometimes
also called granulocytic)
• If the prominent cell line is of the lymphoid
lineage it is a lymphocytic leukaemia.
• A minority of AL may show features of both ALL
and AML (biphenotypic & maybe bilineal such
are called hybrid AL.
ALL CLL Lymphomas MM
naïve
B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes
AML Myeloproliferative disorders
Haematopoietic Myeloid Neutrophils
stem cell progenitor
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Types of leukaemias
Therefore, there are four basic types of leukaemia
1. Acute myeloid leukaemia – AML- (includes myeloblastic,
promyelocytic, monocytic, myelomonocytic, erythrocytic, and
megakaryocytic).
2. Acute lymphoid leukaemia – ALL- (includes T cell, B cell, and Null
cell).
3. Chronic myelocytic leukaemia – CML - (includes myelocytic and
myelomonocytic).
4. Chronic lymphocytic leukaemia – CLL - (includes plasmocytic
{multiple myeloma}, Hairy cell, prolymphocytic, large granular
cell lymphocytic).
Differentiation of acute leukaemias
The following are techniques that can be used to
distinguish AML from ALL in the lab.
• Myeloperoxidase
• Sudan Black B
• Immuno-phenotyping
• Immunocytochemsistry
• Cytogenetics
• Immunoglobulin gene re-arrangement.
• T-cell receptor gene re-arrangement.
Importance of leukaemia differentiation
• It influences the choice of therapy regimen given to
patient.
• Treatment therapy differ significantly in AML and ALL.
• Sub-classification provides prognostic information for
patient management. Eg. ALL is sub-classified into L1- L3
whereas AML is sub-divided into
Mo – M7.
Aetiology of leukaemia
• The exact cause is frequently not known, but predisposing
factors are known:
1. Genetic factors
• Some individuals have an inherited increased pre-disposition to develop
leukaemia. Eg 4 fold increase in risk of CLL in siblings of affected persons.
• There is an increased incidence in those with an inherited tendency for
chromosome fragility or abnormality or those with increased numbers
of chromosomes (such as Down’s syndrome, Klinefelter`s syndrome,
Neurofibromatosis).
• Many of these diseases are characterized by chromosomal
translocations.
• There is an increased incidence in those with hereditary immuno-deficiencies.
2. Chronic marrow diseases
There is an increased incidence in those with chronic marrow dysfunction
such as those with myeloproliferative diseases, myelodysplastic syndromes,
aplastic anaemia, or paroxsymal nocturnal haemoglobinuria.
3. Environmental factors
• Tobacco smoke, ionizing radiation eg; U.V, X-ray
• Exposure to mutagenic chemicals and drugs eg.benzene
• Infectious agents -Viral infections (EBV, HPV, hepatitis B,C etc)
• Dietary -aflatoxins
Incidence of leukaemia
• Acute leukaemias can occur in all age groups
• ALL is more common in children with peak
incidence at 3-7yrs.
• AML is more common in adults
• Chronic leukaemias are usually a disease of adults
• CLL is extremely rare in children and adults below
40 yrs in developed countries except in Africa where
increasing number of young adults develop the
condition.
Comparison Acute Vrs Chronic
leukaemias
Acute Chronic
Age all ages usually adults
Clinical onset sudden insidious
Course (untreated) few wks to 6 mths 2-6 years
Leukaemic cells immature >30% blasts more mature cells
Anaemia prominent mild
Thrombocytopenia prominent mild
WBC count variable increased
Lymphadenopathy mild present; often prominent
Splenomegaly mild present; often prominent
