Detection of Minimal Residual Disease B-Lineage Childhood Acute Lymphoblastic Leukemia by FISH and PCR

Abstract

In ALL, individual chromosomal abnormalities remain strong independent indicators of outcome, especially to indicate risk of relapse (Moorman et al., 2010).Among these abnormalities, those with the most significant impact for risk stratification for treatment are t(9;22)(q34;q11)/BCR-ABL1andt(1;19)(q23;p13.3)/TCF3-PBX1 fusion. The Philadelphia chromosome t(9;22) was associated with an extremely poor prognosis (especially in those who presented with a high WBC count or had a slow early response to initial therapy), and its presence had been considered an indication for allogeneic hematopoietic stem cell transplantation (HSCT) in patients in first remission. The t(1;19) translocation had been associated with inferior outcome in the context of antimetabolite-based therapy, but the adverse prognostic significance was largely negated by more aggressive multiagent therapies. Patients with the t(1;19) translocation had an overall pooroutcome comparable to children lacking this translocation, with a higher risk of CNS relapse and a lower rate of bone marrow relapse, suggesting that more intensive CNS therapy may be needed for these patients . Molecular characterization of the genetic changes has yielded a wealth of information on the mechanism of leukemogenesis. Those findings have also allowed the development of sensitive techniques such as fluorescence in situ hybridization (FISH) for identification of underlying molecular defects, which can be applied to evaluate disease prognosis, monitor response to treatment and predict minimal residual disease. Key words : Acute lymphoblastic leukemia, Minimal residual disease, FISH, PCR, t(9;22)andt(1;19).