4. a) How would you confirm a variant of CML? Take an accurate drug history. Perform cytochemical staining for MPO and PAS. * Verify BCR/ABL fusion using FISH analysis. Perform a bone marrow aspirate. b) The Philadelphia chromosome results from the fusion of which of the following? Chromosomes 8 and 21 Chromosomes 9 and 22 * Chromosomes 8 and 14 Chromosomes 15 and 17 c) The myeloproliferative disorder best described by increased leukocytes, immature granulocytes, and decreased LAP with the Philadelphia chromosome present is which of the following? ET CIMF PV CML * d) A patient's CBC revealed marked leukocytosis with an increased number of immature granulocytes. A few promyelocytes and blasts were seen. There were also an increased number of eosinophils and basophils with rare immature forms. The hemoglobin and hematocrit were normal, but platelets were slightly decreased. Which disorder is associated with these findings? PMF Leukemoid reaction CML * Severe infection
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4) A 59-year-old female has presented clinically with the following: - Weight loss and night sweats - Splenomegaly - Pallor and dyspnoea - Bruising - Complaints of occasional blurry vision Her clinician ordered a full blood count and a general chemistry profile. The following flagged results were returned: Parameter | Result | Reference Range Haemoglobin (Hb) | 94 g/L | 115-160 g/L Red cell count (RCC) | 3.54 x 10^12/L | 3.8-5.2 x 10^12/L Platelets (PLT) | 525 x 10^9/L | 140-400 x 10^9/L White cell count (WCC) | 151.4 x 10^9/L | 4.0-11.0 x 10^9/L Neutrophil count (Neut) | 53 % 80.2 x 10^9/L | 2.0-8.0 x 10^9/L Lymphocyte count (Lymph) | 2 % 3.0 x 10^9/L | 1.0-4.0 x 10^9/L Monocyte count (Mono) | 2 % 3.0 x 10^9/L | 0.1-1.0 x 10^9/L Eosinophil count (Eos) | 6 % 9.0 x 10^9/L | <0.6 x 10^9/L Basophil Count (Baso) | 3 % 4.5 x 10^9/L | <0.2 x 10^9/L Metamyelocytes | 15 % 22.7 x 10^9/L | Myelocytes | 14 % 21.2 x 10^9/L | Promyelocytes | 3 % 4.5 x 10^9/L | Blasts | 2 % 3.0 x 10^9/L | Nucleated RBC (NRBC) | 2 Per 100/WCC | Morphology | Leucocytosis with a full spectrum of immature and mature myeloid cells. Myeloid cells have normal morphology. Red blood cells are normochromic and normocytic. | Neutrophil alkaline phosphatase score | Markedly decreased | Uric acid (Urate) | 0.59 mmol/L | 0.15 - 0.40 mmol/L Lactate dehydrogenase (LDH) | 646 U/L | 120 - 250 U/L From these results, her clinician requested a bone marrow biopsy for chromosomal analysis. a) Given the results indicate above, what type of leukaemia would you expect this patient to have? b) What abnormality/result would you expect cytogenetic analysis to show and what specific type of chromosomal alteration is this?
Supreeta N.
A bone marrow was performed on Khadeejah. The marrow showed a cellularity of about 75%. There was myeloid hyperplasia with 9% blasts, 26% promyelocytes, 18% myelocytes, 6% metamyelocytes, 4% bands, and 37% eosinophils. The ratio of myeloid-to-erythroid precursors (M:E) was 12:1. The myelocytes were hypogranular, and some had two nuclei. The erythroid precursors showed megaloblastoid changes. Megakaryocytes were adequate in number but showed abnormal forms with nuclear separation and single nucleated forms. 7. Which of the hematopoietic cell lines exhibit dyshematopoiesis in the bone marrow? 8. How would you classify the bone marrow cellularity? Why? 9. Identify at least two features of the bone marrow that are compatible with the diagnosis. 10. What chemistry tests would be helpful to rule out megaloblastic anemia? 11. How would you treat this particular patient?
Madhur L.
A female patient 19 years old, whose symptoms are anemia and internal bleeding due to a massive buildup of leukemic white blood cells, is diagnosed with chronic myelogenous leukemia (CML). Karyotype analysis shows that the leukemic cells of this patient are heterozygous for a reciprocal translocation involving chromosomes 9 and $22 .$ However, none of the normal, nonleukemic cells of this patient contain the translocation. Which of the following statements is true and which is false? a. The translocation results in the inactivation (loss of function) of a tumor-suppressor gene. b. The translocation results in the inactivation (loss of function) of an oncogene. c. There is a $50 \%$ chance that any child of this patient will have CML. d. This patient is a somatic mosaic in terms of the karyotype. e. DNA extracted from leukemic cells of this patient, if taken up by normal mouse tissue culture cells, could potentially transform the mouse cells into cells capable of causing tumors. f. The normal function of the affected tumor-suppressor gene or proto-oncogene at the translocation breakpoint could potentially block the function of the cyclin proteins that drive the cell cycle forward. g. Two rare events must have occurred to disrupt both copies of the tumor-suppressor gene or proto-oncogene at the translocation breakpoint in the leukemic cells. h. A possible treatment of the leukemia would involve a drug that would turn on the expression of the tumor-suppressor gene or oncogene at the translocation breakpoint in the leukemic cells.
Adi S.
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