1. Hematology There are four lectures: 1.Acute leukemias (2 hours). 2.Chronic leukemias (2 hours).

2. Acute leukemias أ. م. د. محمد شنين علي العبادي معاون عميد كلية الطب / جامعة كربلاء ورئيس فرع الامراض والطب العدلي M. B. Ch. B. & F. I. C. P.(Hematopathology) الثلاثاء 2015/3/30 الساعة الحادية عشرة والنصف صباحا

3. Definition and classification of acute leukemias Definition: Acute leukemias are blast cell malignancies or malignancies of immature hemopoietic cells. Classification: 1.Acute myeloid (myeloblastic) leukemia (AML) 2.Acute lymphoid (lymphoblastic) leukemia (ALL). 3.Mixed AML+ALL.

4. Aetiology of acute leukemias 1.Ionizing radiation(x-rays, atomic bombs &radiotherapy for lymphoma may cause acute leukemia) 2.Chemicals: Chronic exposure to benzene or treatment with alkylating agents like melphalan for myeloma may cause acute leukemia. 3.Chromosomal abnormalities: traslocations are found in many cases of leukemias.

5. Pathogenesis and Pathophysiology of acute leukemias The exact pathogenesis is unknown, but there is a clear switching-off mechanisms which cut the differentiation of blasts or promyelocytes to mature cells. The drug ATRA (All Trans Retinoic Acid) is a drug for a witching-on and very successful for treatment of AML, M 3 subtype.

6. Abnormal cells (blasts) proliferate rapidly inside the bone marrow, infiltrating nearly all the marrow (reflected in blood samples as pancytopenia, clinically 3P) then they will go to peripheral blood and enter (infiltrate) liver, spleen, lymph nodes, testes, skin, & other organs (reflected as organomegaly). 3P: Pallor, pyrexia, purpura. Pathogenesis and Pathophysiology of acute leukemias

7. Laboratory diagnosis of acute leukemias 1.CBP(CBC),ESR,Blood film,&reticulocyte count Results: Low Hb, low platelets,High WBC count, rarely low. The most important point is the presence of blasts or promyelocytes (30% or more of total WBC in the peripheral blood or in the bone marrow or both), ESR high or normal, retic.count low or normal.

8. 2. Bone marrow aspiration is usually diagnostic for acute leukemias. The marrow is usually infiltrated by blasts with evident suppression of normal hemopoietic elements(low erythropoiesis, low megakariocytes and low normal myelopoiesis) while the abnormal myeloid series (abnormal cells or blasts) are increased. Laboratory diagnosis of acute leukemias

9. Subclassification of acute leukemias 1.AML subclasses M 0 : No maturation & no differentiation of myeloblasts is seen. M 1 : Maturation can be seen, but below 10%. M 2 :Maturation of myeloblasts reaches 10-20%. M 3 :Acute promyelocytic leukemia (APL). M 4 : Myelomonocytic leukemia (monocytes >1000/mm 3 together with 30% or more of blasts. M 5 : M5 a :acute monoblastic and M5 b :acute monocytic leukemia M 6 : Erythroblastic leukemia. M 7 : Megakarioblastic leukemia.

10. 2. ALL subclasses According to cell type affection: B-ALL (B lymphocyte or B-cell leukemia) T-ALL (T lymphocyte or T-cell leukemia) Old classification L 1, L 2, & L 3 according to the morphological differences. Subclassification of acute leukemias

11. Q. Why do we need such subclassification? Answer: 1.To specify treatment. Treatment of ALL is different than that of AML. Again treatment of subclasses of AML is different. 2. To predict the prognosis. B-ALL carries better prognosis than T-ALL Subclassification of acute leukemias

12. Q. What is the best way for subclassification? Answer: The best way is by using (MIC) M:morphology of blasts. I: immunophenotyping (surface marker studies or called CD markers(Cluster of differentiation) of blast cells) C : cytogenetics i.e detecting the types of translocations since some translocations are specific for certain type or subtype of leukemia. Subclassification of acute leukemias

13. Morphology of blasts 1. Myeloblasts are large cells with high N/C ratio, open chromatin pattern, clear 1-3 nucleoli, cytoplasmic granules or diagnostic cytoplasmic rods which are called Auer rods or no granules and no rods. 2. Lymphoblasts are large cells with high N/C ratio, open chromatin pattern, unclear few nucleoli, no granules and no Auer rods. Subclassification of acute leukemias

14. Immunophenotyping Studying the blast cells surface markers since each cell has certain surface glycoprotein or CD markers (cluster of differentiation) Positive blasts for CD 13,CD 14,& CD 33 is diagnostic for AML Positive blasts for CD 19 & CD 22 is diagnostic for B- ALL Negative blasts for CD 19 & CD 22 and positive for CD 3 & CD 7 is diagnostic for T-ALL Subclassification of acute leukemias

15. Morphology of acute leukemia Auer rod is diagnostic of AML.

16. AML: Clear 1-3 nucleoli Morphology of acute leukemia

17. Unclear nucleoli and open chromatin pattern ALL or undifferentiated AML Morphology of acute leukemia

18. Thank you