BCR-ABL Essay

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Detection of BCR-ABL positive cells in an asymptomatic patient: A Case Report and Literature Review
Soley Bayraktar1,2, MD, Mark Goodman1, MD
Abstract: We report a case of an asymptomatic 39-year old male who was incidentally found to have a white blood cell count of 15.000/mm3 associated with a positive BCR-ABL/t(9;22)(q34;q11) chromosomal translocation detected in 51/300 of cells by FISH and RT-PCR from peripheral blood. Within the next 3 months, leukocytosis spontaneously subsided; however BCR-ABL by RT-PCR and FISH was persistent both in peripheral blood and bone marrow. The patient was not started on any therapy and is being followed regularly with laboratory check up and physical examination for monitoring signs and symptoms of chronic myeloid leukemia (CML) and biological behavior of his BCR-ABL transcripts. At 1 year of surveillance, he is disease free; however he has persistent detection of BCR-ABL fusion gene. Our case is challenging because actual risk of developing CML in BCR-ABL positive healthy, asymptomatic patients is not known.
Keywords: CML, Philadelphia chromosome, FISH, RT-PCR.
INTRODUCTION
Chronic myeloid leukemia (CML) is a myeloproliferative disorder with an incidence of 2 cases per 100,000 people and represents 7-20% of all leukemia cases.[1] Although is an uncommon entity, CML is one of the few leukemias that has a defined pathogenesis; which involves the Philadelphia chromosome (Ph)/t(9;22)(q34;q11) chromosomal translocation and activated tyrosine kinases (TK) in the mutated hematopoietic stem cell.[2] Also, it is one of the first leukemias in which a rational targeted therapy with tyrosine kinase inhibitors (TKI) revolutionized the treatment and natural history of the disease by improving overall survival (OS) with long term remissions.[1,3] Although it was once to be thought to be pathognomonic for CML, evidence of BCR-ABL fusion gene or t(9;22)(q34;q11) translocation is also found in approximately in one-third of cases of ALL and < 1% of AMLs.[4,5] Moreover, there is a substantial group of asymptomatic, healthy people who can bare this chromosomal aberration and never develop CML.[5-7] As of now, there are no guidelines for stratification of the risk factors for CML development, monitoring BCR-ABL transcripts and establishing a proper treatment in this subgroup. We report a case of an asymptomatic 39-year old male who was found to have white blood cell (WBC) count of 15.000/mm3 without therapy yet, associated with a positive BCR-ABL translocation and subsequent normalization of his leukocytosis with persistence of the BCR-ABL detection in peripheral blood (PB) and bone marrow (BM) cells. We provide a detailed clinical analysis in conjunction with a brief literature review.
CASE REPORT
The patient is a 39-year-old Jamaican man who was found to have elevated WBC of 15.000/mm3 with normal differential, as an incidental finding during a follow-up visit to his primary care physician. Review of systems were negative including fever/chills, weight loss, night sweats and bleeding. Past medical history was significant for hypertension and diabetes mellitus type II. On physical examination, there were no palpable enlarged lymph nodes, organomegaly or signs of bleeding. Complete Blood Count (CBC) showed WBC of 15.000/mm3 with normal differential, hemoglobin (Hb) and hematocrit (Htc) of 15 mg/dl and 45%, and platelets of 308.000/mm3. The peripheral blood smear showed normal neutrophils, no myelocytes, metamyelocytes, nucleated red blood cells or giant platelets. Metaphase cytogenetic analysis of PB did not demonstrate any karyotype abnormalities; however BCR/ABL t(9;22) was detected in 51 of 300 cells by Fluorescence In-Situ Hybridization (FISH) and quantitative real time PCR (RT-PCR). There were no evidence of other cytogenetic or molecular abnormalities. Further work-up with CT-chest/abdomen/pelvis did not reveal any systemic disease. At that time, no specific treatment was recommended and a
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