WBR0185

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1], Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics, MainCategory::Pathology
Sub Category	SubCategory::Oncology
Prompt	[[Prompt::An 7-year-old boy is brought by his parents to the emergency department for severe left leg pain that started 2 days prior to presentation. His mother reports that the child has been very tired for the past few weeks. She also explains that her son has lost a lot of weight, and has been running out of breath with minimal activity recently. Upon further questioning, the child denies any trauma to his leg. On physical exam, you notice an ill appearing child with abdominal swelling and petechiae on the upper and lower extremities. A CBC is drawn and shows a hemoglobin of 8.5 g/dL, hematocrit of 25, and a WBC count of 75,000/uL. Which of the following findings is considered a good prognostic marker in this patient?]]
Answer A	AnswerA::t(12;21) translocation
Answer A Explanation	AnswerAExp::t(12;21) translocation is associated with a favorable prognosis and a lower relapse rate in patients with ALL.
Answer B	AnswerB::t(11;22) translocation
Answer B Explanation	AnswerBExp::t(11;22) translocation is not common among patients with ALL. It is classically associated with Ewing’s sarcoma.
Answer C	AnswerC::Ten-eleven translocation 2 (TET2) mutation
Answer C Explanation	AnswerCExp::Ten-eleven translocation 2 (TET2) is a gene located on chromosome 4q24. Mutations involving this gene are found in myeloid malignancies including myelodysplastic syndromes, CML, AML. It is not a prognostic indicator in ALL.
Answer D	AnswerD::Terminal deoxynucleotidyl transferase (TdT) positivity
Answer D Explanation	AnswerDExp::TdT is a protein expressed early in the development of pre-T and pre-B cells but it is not a prognostic marker of the disease.
Answer E	AnswerE::Isocitrate dehydrogenase 1/2 (IDH1/IDH2) mutation
Answer E Explanation	[[AnswerEExp::Isocitrate dehydrogenase 1 (IDH1) is a gene located in chromosome 2q33.3 while IDH2 is located in chromosome 15q26.1. These genes are responsible for encoding enzymes catalyzing oxidative decarboxylation of isocitrate to alpha ketoglutarate. Mutations in this gene confer poor prognosis in certain subsets of AML.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, accounting for approximately 30% of all cancers in patients younger than 14 years of age. It is a clonal lymphoid stem cell disease. The classical presentation of patients with ALL includes fatigue, recurrent infections, bony pain, weight loss, easy bruisability, petechiae, dyspnea on exertion, and hepatosplenomegaly. t(12;21) translocation is the most common chromosomal anomaly in childhood leukemias and is exclusively found in patients with Pre-B-ALL (approximately 25% of these patients). The translocation generates TEL-AML1 (ETV6-RUNX1) fusion gene, which is associated with a more favorable prognosis as evidenced by a significantly lower relapse rate. Evaluation of this and other prognostic markers helps in selecting low toxicity versus high toxicity therapies. Educational Objective: The t(12;21) translocation is a good prognostic marker in cases of acute lymphoblastic leukemia. References: Romana SP, Mauchauffé M, Le coniat M, et al. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood. 1995;85(12):3662-70. Borkhardt A, Cazzaniga G, Viehmann S, et al. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group. Blood. 1997;90(2):571-7.]]
Approved	Approved::Yes
Keyword	WBRKeyword::ALL, WBRKeyword::Lymphoblast, WBRKeyword::Blasts, WBRKeyword::TdT, WBRKeyword::t(12;21), WBRKeyword::Acute Lymphocytic Leukemia, WBRKeyword::Translocations, WBRKeyword::Prognosis, WBRKeyword::Genetic anomalies, WBRKeyword::Pediatric cancers
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