CML leukemia pathology ppt mbbs 2nd year.pptx

Ppt

1. Chronic myeloid leukaemia (CML) Submitted by:- Ansu Paloh 22MBBS006

2. Circulating blood normally contains 3 main types of mature blood cells:- Erythrocytes/Red blood cells Leucocytes/White blood cells Thrombocytes/Platelets

3. WBCs:- Granulocytes – ~Depending upon the colour and content of granules , it is of three types- Neutrophils Eosinophils Basophils Agranulocytes - B&T lymphocytes Monocyte

4. Haematopoietic stem cell (HSC) differentiate into two types of progenitors:- Lymphoid stem cells , develops into B&T lymphocytes NK cells 2. Nonlymphoid or Myeloid( trilineage ) stem cells Granulocyte-monocyte progenitors ( producing neutrophils, eosinophils and monocytes). Erythroid progenitors (producing red cells ). Megakaryocytes(producing platelets).

5. HSC Lymphoid stem cells. Myeloid( trilineage ) stem cells Prolymphocyte . Granulocyte-monocyte . Erythroid p. Megakaryocytes T&B lymphocytes, Nkcells . Neutrophils. RBC. Platelets. Eosinophils Basophils Monocytes

6. Granulopoiesis Lymphopoiesis

7. Myeloid series:- Myelomonoblast (most primitive precursor) Myeloblast Promyelocyte Myelocyte Metamyelocyte Band forms Neutrophil

8. Chronic myeloid leukaemia:- Definition:- CML is an acquired disease of haematopoietic stem cells that is characterized by leucocytosis with granulocytic immaturities , splenomegaly , basophilia , distinct chromosomal abnormality (Philadelphia chromosome).

9. Age Most commonly occurs in old age [ >50yrs]

10. Pathogenesis In translocation ABL gene (normally located on chromosome9) | Translocated to chromosome22 | It fuses with BCR (Break point cluster) gene. | BCR-ABL hybrid gene (Philadelphia chromosome)

11. | 210 KDa fusion protein | Abnormal signal transduction even without growth factors / Abnormal tyrosine kinase activity | Uncontrolled mitosis | CML

12. Phases of CML ~ Triphasic Leukaemia Chronic Phase Accelerated phase Blast phase Bone marrow and peripheral blood, <10% blast cells Blast cells, 10-19% Blast count,>20% Basophilia ~ 10% Leucocytosis association with thrombocytosis or thrombocytopenia and splenomegaly. Blast cells may be myeloid, Lymphoid, erythroid. Myeloid blast crisis in CML is more common and resembles AML but is devoid of Auer rods that are seen in myeloblasts of AML.

13. Clinical features:- Anaemia producing pallor , lethargy, dyspnoea. Bleeding manifestations causing spontaneous bruises , petechiae and bleeding from gums. Infections Symptoms due to hypermetabolism such as wt.loss , anorexia, lasstutude , night sweats. Splenomegaly is massive.

14. LAB Diagnosis:- Blood picture: Anaemia [Normocytic normochromic. Thrombocytopenia White blood cell Marked leucocytosis approx. 200,000/ microlitre Immature Neutrophils [band forms , metamyelocyte , myelocytes , promyelocytes ]. Basophilia Eosinophilia

15. 2. Bone marrow examinations Cellularity, hypercellularity proliferating myeloid cells. Myeloid cells predominate in the bone marrow with increased myeloid-erythroid ratio. Erythropoiesis reduced Megakaryocytes are normal or smaller in size.

16. 3. Cytogenetics :- ~Characteristics Philadelphia chromosome seen in 90-95% cases of CML. 4. Cytochemistry :- ~ Reduced scores of neutrophil alkaline phosphatase(NAP), one of the factor which helps to distinguish CML from Myeloid leukamoid reaction (in which NAP scores are elevated).

17. 4. Other Investigation :- Elevated serum B12 and vitamin B12 binding capacity. Elevated serum uric acid ( hyperuricaemia )

18. Treatment:- Treatment of Anaemia and haemorrhage- a, Anaemia & Haemorrhage- fresh blood transfusion and platelet concentrates. b, Patients with severe thrombocytopenia- Platelet transfusion. 2. Imatinib Oral Therapy – a, It competitively inhibit ATP binding site of the ABL Kinase . Inhibit signal transduction BCR-ABL fusion protein. b, Induces apoptosis in BCR – ABL positive cells. 3. Allogenic bone marrow (stem cell) transplantation.

19. Thank you!