Leukemia

1. Leukemia

2. Leukemia • A group of malignant disorders affecting the blood and blood-forming tissues of • Bone marrow • Lymph system • Spleen • Occurs in all age groups

3. :Epidemiology CML occurs in all age groups, but most commonly in the middle-aged and elderly. Its annual incidence is 1–2 per 100,000 people, and slightly more men than women are affected. CML represents about 15–20% of all cases of adult leukemia in Western populations.The only well-described risk factor for CML is exposure to ionizing radiation; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki[16

4. Leukemia • Results in an accumulation of dysfunctional cells because of a loss of regulation in cell division • Fatal if untreated • Progressive

5. Leukemia • Often thought of as a childhood disease • The number of adults affected with leukemia is 10 times that of children

6. Leukemia Etiology and Pathophysiology • No single causative agent • Most from a combination of factors • Genetic and environmental influences

7. Leukemia Etiology and Pathophysiology • Associated with the development of leukemia • Chemical agents • Chemotherapeutic agents • Viruses • Radiation • Immunologic deficiencies

8. Leukemia Classification • Acute versus chronic • Cell maturity • Acute: • Chronic:

9. Acute leukemia is characterized by a rapid increase in the number of immature blood cells there are. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children. Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

10. Leukemia Classification • Type of white blood cell (WBC) • Acute lymphocytic leukemia (ALL) • Acute myelogenous leukemia (AML) • Also called acute nonlymphoblastic leukemia (ANLL) • Chronic myelogenous leukemia (CML) • Chronic lymphocytic leukemia (CLL)

11. Myelogenous Leukemia • Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating blood

12. Myeloid tissue is a biologic tissue with the ability to perform hematopoiesis. It is mainly found as the red bone marrow in bones, and is often synonymous with this. However, myeloid can also be present in the liver and spleen . • A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not in circulating blood (except when caused by certain diseases).

13. Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm.[1] They are also called polymorphonuclear leukocytes (PMN or PML) because of the varying shapes of the nucleus, which is usually lobed into three segments. • The myeloblast is a unipotent stem cell, which will differentiate into one of the actors of the granular series.

14. Acute Myelogenous Leukemia (AML) • Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating blood • One fourth of all leukemias • 85% of the acute leukemias in adults • Abrupt, dramatic onset • Serious infections, abnormal bleeding • Uncontrolled proliferation of myeloblasts • Hyperplasia of bone marrow and spleen

15. Chronic Myelogenous Leukemia (CML) • Excessive development of mature neoplastic granulocytes in the bone marrow • Move into the peripheral blood in massive numbers • Ultimately infiltrate the liver and spleen

16. Chronic Myelogenous Leukemia • Philadelphia chromosome • The chromosome abnormality that causes chronicmyeloidleukemia (CML) (9 &22) • Genetic marker • Chronic, stable phase followed by acute, aggressive (blastic) phase

17. Leukemia Clinical Manifestations • Relate to problems caused by • Bone marrow failure • Overcrowding by abnormal cells • Inadequate production of normal marrow elements • Anemia, thrombocytopenia, ↓ number and function of WBCs

18. Leukemia Clinical Manifestations • Relate to problems caused by • Leukemic cells infiltrate patient’s organs • Splenomegaly • Hepatomegaly • Lymphadenopathy • Bone pain, meningeal irritation, oral lesions (chloromas)

19. It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome

20. CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists from Philadelphia,Pennsylvania:

22. This exchange brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia virus) on chromosome 9. The resulting hybrid gene BCR-ABLcodes for a fusion protein with tyrosine kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth.

23. The Philadelphia chromosome: T (9:22) translocation. The Ph chromosome is a shortened chromosome 22, which result from Reciprocal translocation between the long arms of chromosomes 9 & 22 ,The result is a hybrid bcr-abl gene (fusion protein) with increased tyrosine Kinaseacm resulting in leukemic transformation.