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1
 Name: Abdul Qader
 Medical lab Technologist
 Rehman college of Allied Health Science
 Email: qadarkhan260@gmail.com
2
Topic:
Molecular biology of leukemia
3
History
 Rudolf Virchow, a German biologist discovered leukemia in
1845. while performing an autopsy , he noticed a high number
of white blood cells in the dead body person’s bloodstream.
For this condition, Virchow suggested the Greek name
leukemia, which means “White blood”.
 The term “ Myeloid “ was invent by Franz Christian Neumann
in 1869
 1900- Otto Naegeli who divided the leukemia into myeloid
and lymphoid steps
4
Words Abbreviation
N-ras gene Neuroblastoma RAS gene
RB1 gene Retinoblastoma 1 gene
Tal-1 T-cell acute lymphocytic leukemia 1
Ttg-2 Tissue transglutaminase 2
HOX-11 Homeobox-11
ABL Abelson
BCR breakpoint cluster region
Bcl-1 gene B-cell lymphoma gene
FISH Fluorescence in situ hybridization
CSF Cerebrospinal fluid
PCR Polymerase chain reaction
CBC Complete blood count
5
Introduction
 Leukemia is characterized by hyperproliferation of
immature white blood cells
• Normally, the rate of new cell growth and old cell death are
kept in balance
• In leukemia, this balance is disturbed
1) Uncontrolled cell’s growth
2) Loss of cell’s ability to undergo apoptosis (cell death)
6
• Normal person Leukemic patient
• Red
Blood
Cell
• White
Blood Cell Hyperproliferation of white
blood cell
7
Type of Cell Affected
There are two main types of white blood cells:
o Lymphocytes
o Granulocytes
 Leukemia involving lymphocytes is called lymphocytic leukemia.
 Leukemia involving granulocytes is called myeloid or
myelogenous leukemia.
8
9
Acute Leukemia :
 In Acute leukemia malignant transformation occurs in the
haemopoietic stem cell
 The presence of 20% of blast cells in the blood
 Less than 20% blasts cytogenetic or Molecular genetics
abnormalities are present
 Progress rapidly
 Common in younger age
 Short clinical course (weeks to months)
10
Types of Acute leukemia
There are two types of acute leukemia
 Acute myeloid leukemia - (AML)
 Acute lymphoblastic leukemia - (ALL)
11
Acute myeloid leukemia
 Acute myeloid leukemia (AML) is a malignant disease of the
bone marrow in which excessive production of immature
myeloblast cells.
 80% in adult
 In 30% cases have N-ras-gene mutation
 25% cases have RB1 gene
12
Acute lymphoblastic leukemia-ALL
 Commonest form of malignancy in childhood
 Peak incidence at 4-5 years of age
 Acute onset with short history of duration
 85% are B cell , 15% are T cell
13
Acute lymphoblastic leukemia-ALL
 10-25% cases have abnormalities of N-ras gene
 20-25 % have fusion of the tal-1 gene
 Less frequently involved tal-2, Ttg-2 , HOX-11 genes
14
Chronic leukemia
 In chronic leukemia the leukemia cells are more mature cells, but they
are not completely normal. They generally do not fight infection as well
as normal WBCs
 Progress slowly
 Common in older age
 Longer clinical course (years)
15
Types of chronic leukemia
There are two types of Chronic leukemia
 Chronic myeloid (or myelogenous) leukemia (CML)
 Chronic lymphocytic leukemia (CLL)
16
Chronic myeloid leukemia (CML)
 Myeloid leukemia (myelogenous ) also known as granulocytic
leukemia is a cancer of the white blood cells.
 It is a clonal disorder of a stem cell
 Common in adults
 The pathogenesis of CML involving the fusion of the ABL-gene
on chromosome 9 and BCR-gene on chromosome 22
17
Chronic lymphocytic leukemia (CLL)
 Chronic neoplastic disorder characterized by accumulation of
small mature –looking lymphocytes which are immunologically
immature in blood , bone marrow and lymph nodes.
 Occur in older patients (>50 year old)
 Abnormalities of p53 and bcl-1 gene
18
19
Risk Factors:
 Smoking
 Genetic disorder
 Radiation
 Chemotherapy
 Chemicals
20
Clinical feature :
 Bycytopenia :
• Hb- anemia
• Platelets
 Organ infiltration:
• Lymphadenopathy
• Splenomegaly more common with ALL than AML
• Hepatomegaly
21
Diagnosis:
 CBC
 peripheral smear
 Bone marrow
 Cytogenetic
 FISH
 PCR
 Immunohistochemistry
22
Treatment :
 Chemotherapy
 Radiotherapy
 Bone marrow transplant
23
24

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Leukemia

  • 1. 1
  • 2.  Name: Abdul Qader  Medical lab Technologist  Rehman college of Allied Health Science  Email: qadarkhan260@gmail.com 2
  • 4. History  Rudolf Virchow, a German biologist discovered leukemia in 1845. while performing an autopsy , he noticed a high number of white blood cells in the dead body person’s bloodstream. For this condition, Virchow suggested the Greek name leukemia, which means “White blood”.  The term “ Myeloid “ was invent by Franz Christian Neumann in 1869  1900- Otto Naegeli who divided the leukemia into myeloid and lymphoid steps 4
  • 5. Words Abbreviation N-ras gene Neuroblastoma RAS gene RB1 gene Retinoblastoma 1 gene Tal-1 T-cell acute lymphocytic leukemia 1 Ttg-2 Tissue transglutaminase 2 HOX-11 Homeobox-11 ABL Abelson BCR breakpoint cluster region Bcl-1 gene B-cell lymphoma gene FISH Fluorescence in situ hybridization CSF Cerebrospinal fluid PCR Polymerase chain reaction CBC Complete blood count 5
  • 6. Introduction  Leukemia is characterized by hyperproliferation of immature white blood cells • Normally, the rate of new cell growth and old cell death are kept in balance • In leukemia, this balance is disturbed 1) Uncontrolled cell’s growth 2) Loss of cell’s ability to undergo apoptosis (cell death) 6
  • 7. • Normal person Leukemic patient • Red Blood Cell • White Blood Cell Hyperproliferation of white blood cell 7
  • 8. Type of Cell Affected There are two main types of white blood cells: o Lymphocytes o Granulocytes  Leukemia involving lymphocytes is called lymphocytic leukemia.  Leukemia involving granulocytes is called myeloid or myelogenous leukemia. 8
  • 9. 9
  • 10. Acute Leukemia :  In Acute leukemia malignant transformation occurs in the haemopoietic stem cell  The presence of 20% of blast cells in the blood  Less than 20% blasts cytogenetic or Molecular genetics abnormalities are present  Progress rapidly  Common in younger age  Short clinical course (weeks to months) 10
  • 11. Types of Acute leukemia There are two types of acute leukemia  Acute myeloid leukemia - (AML)  Acute lymphoblastic leukemia - (ALL) 11
  • 12. Acute myeloid leukemia  Acute myeloid leukemia (AML) is a malignant disease of the bone marrow in which excessive production of immature myeloblast cells.  80% in adult  In 30% cases have N-ras-gene mutation  25% cases have RB1 gene 12
  • 13. Acute lymphoblastic leukemia-ALL  Commonest form of malignancy in childhood  Peak incidence at 4-5 years of age  Acute onset with short history of duration  85% are B cell , 15% are T cell 13
  • 14. Acute lymphoblastic leukemia-ALL  10-25% cases have abnormalities of N-ras gene  20-25 % have fusion of the tal-1 gene  Less frequently involved tal-2, Ttg-2 , HOX-11 genes 14
  • 15. Chronic leukemia  In chronic leukemia the leukemia cells are more mature cells, but they are not completely normal. They generally do not fight infection as well as normal WBCs  Progress slowly  Common in older age  Longer clinical course (years) 15
  • 16. Types of chronic leukemia There are two types of Chronic leukemia  Chronic myeloid (or myelogenous) leukemia (CML)  Chronic lymphocytic leukemia (CLL) 16
  • 17. Chronic myeloid leukemia (CML)  Myeloid leukemia (myelogenous ) also known as granulocytic leukemia is a cancer of the white blood cells.  It is a clonal disorder of a stem cell  Common in adults  The pathogenesis of CML involving the fusion of the ABL-gene on chromosome 9 and BCR-gene on chromosome 22 17
  • 18. Chronic lymphocytic leukemia (CLL)  Chronic neoplastic disorder characterized by accumulation of small mature –looking lymphocytes which are immunologically immature in blood , bone marrow and lymph nodes.  Occur in older patients (>50 year old)  Abnormalities of p53 and bcl-1 gene 18
  • 19. 19
  • 20. Risk Factors:  Smoking  Genetic disorder  Radiation  Chemotherapy  Chemicals 20
  • 21. Clinical feature :  Bycytopenia : • Hb- anemia • Platelets  Organ infiltration: • Lymphadenopathy • Splenomegaly more common with ALL than AML • Hepatomegaly 21
  • 22. Diagnosis:  CBC  peripheral smear  Bone marrow  Cytogenetic  FISH  PCR  Immunohistochemistry 22
  • 23. Treatment :  Chemotherapy  Radiotherapy  Bone marrow transplant 23
  • 24. 24