Question

A 58-year-old white man presented to his physician for evaluation of leukocytosis found incidentally on a complete blood count performed at a health fair. He had no current complaints, but when questioned, reported felling of fullness in the left upper quadrant of his abdomen. He reported no recent fevers night sweats, or weight loss. He worked as a supervisor in an automobile assembly plant. On physical examination, he was found to have splenomegaly, with the spleen tip barely palpable below the costal margin, no hepatomegaly or lymphadenopathy was found.

Complete blood count (CBC) showed WBC 51,200/µL, hemoglobin 13.1 g/dL, hematocrit 38.4%, MCV 90.7, and platelet count 610,000/µL. WBC differential showed 64% segmented neutrophils, 8% bands, 5% lymphocytes, 4% monocytes, 4% eosinophils, 5% basophils, 2% metamyelocytes, 7% myelocytes, 1% promyelocytes, and 1 nucleated RBC. LAP score was decreased.

A bone marrow aspirate and biopsy were performed and showed a markedly hypercellular bone marrow with marked granulocytic hyperplasia and moderate megakaryocytic hyperplasia. Blasts constituted 6% of the cells present. Bone marrow cytogenetiics performed showed 46,XY,t(9;22) (q34.1;q11.2); that is, a Phyladelphia chromosome was present.

Treatment was begun with interferon-alpha and low-dose cytarabine with good hematologic response. However, the patient subsequently had difficulty tolerating the treatment because of fever and malaise, and was temporarily lost to follow-up.

He returned 18 months later complaining of fatigue and fevers. Physical examination showed increasing splenomegaly as well as hepatomegaly. At this time, his CBC showed WBC 98,800/µL, hemoglobin 11.6 g/dL, hematocrit 34.9%, MCV 89.0 fL and platelet count 1,070,000/µL. WBC differential showed 48% segmented neutrophils, 8% bands, 3% lymphocytes, 4% monocytes, 3% eosinophils, 21% basophils, 3% metamyelocytes, 8% myelocytes, 2% blasts, and 2 nucleated RBCs. A repeat bone marrow aspirate again showed marked granulocytic and moderate megakaryocytic hyperplasia, now with 14% blasts.

Treatment was begun with imatinib mesylate (Gleevec®), which had recently become available. The patient’s WBC count decreased and symptoms disappeared within a few weeks. He subsequently achieved complete hematologic and compete cytogenetic remission. RT-PCR analysis of the patient’s bone marrow specimens continued to show the presence of BCR-ABL fusion gene product, but he remained asymptomatic and incomplete hematologic remission 3 years later.

QUESTIONS:

1. The translocation that results in the Philadelphia chromosome is between chromosomes:
   1. 21 and 22
   2. 9 and 22
   3. 8 and 14
   4. 9 and 21
2. The blast phase of CML is:
   1. Followed by the chronic phase and the accelerated phase
   2. Seen only in atypical CML
   3. The terminal phase of CML, characterized increased blasts (>20%) in the blood and bone marrow
   4. The earliest phase seen in typical CML
3. All of the following favors a diagnosis of CML over leukemoid reaction except:
   1. Absence of basophils and eosinophils in the peripheral blood
   2. A low LAP score
   3. Ph chromosome
   4. And enlarged spleen
4. The only proven curative treatment for CML at this time is:
   1. Combination interferon-alpha with low0dose cytarabinel
   2. Imatinib mesylate (Gleevec®)
   3. Bone marrow transplantation
   4. CML is not curable
5. At the molecular level, the aberrant conjoining of material from chromosome 9 and chromosome 22 results in a fusion gene called:
   1. BCR-ABL gene
   2. JAK2 gene
   3. p53
   4. The blast transformation gene
6. When the above patient returned after being lost to follow-up for 18 months he was in:
   1. Chronic phase
   2. Accelerated phase
   3. Blast phase
   4. Jersey City
7. The worst prognosis in patients with CML is associated with:
   1. Thrombocytosis
   2. Blast phase
   3. The presence of the Ph chromosome
   4. Splenomegaly

Answer 1

The answer to these mcq questions are

Question 1

The translocation that result in Philadelphia chromosome occur between 9 and 22

So the correct answer is option B

In philadelphia chromosome . There is reciprocal translocation of long arm of chromosome 22 and the long arm of chromosome 9

it can be written as t(9;22)

Question 2

the blast phase is the terminal phase of CML which is characterized by increased blast (more than 20percent ) in blood and bone marrow

so correct answer is option C

There are 3 stages in CML

1st chronic stage followed by accelerated phase and then blastic phase which is the last phase of CML

the blast cells may be myloid lymphoid erythroid or undifferentiated and are established by morphology cytochemistry , or immunophenotyping .

question 3

all of the following favour CML over leukaemia reaction except

option A

absence of basophils and eosinophils in peripheral blood films

this statement about CML is wrong as in CML we can see basophil and eosinophils in peripheral blood films

there is marked splenomegaly in CML .Which is absent in leukaemoid reaction

LAP score is reduced in CML and elevated in leukemoid reaction

ph chromosome is present in CML NOT IN LEUKAEMOID REACTION

SO option A is correct answer

question 4

the only proven curative treatment of CML is

bone marrow or stem cell transplantation

so correct option is option C

imatinib and other drug therapy are not proven to cure CML

interferon alpha were drug of choice before bone marrow transportation

bone marrow transplantation is proven curable to CML but it is confined to fraction of patient which mainly include young age and those who get matched donor . There is risk of graft vs host disease

Question 5

Fusion of chromosome 9 and 22 result in the gene is called BCR/ ABL gene

Ao correct option is A

Hope you find this helpful thankyou ☺️?