Clinical implications of cytogenetic and molecular analyses of pediatric acute lymphoblastic leukemia

The prognosis for children with acute lymphoblastic leukemia (ALL) has improved steadily over the past 20 years. Today, at least two-thirds of newly diagnosed cases are curable with intensified risk-based therapy. The challenge now is to identify, prior to or early in treatment, the one-third of patients who are destined to relapse, so that alternative therapy can be introduced sooner. Cytogenetic studies of lymphoblasts have identified recurring abnormalities of prognostic importance and pinpointed chromosomal regions for molecular analyses. Recently, molecular diagnostic techniques have been developed for the more common cytogenetic subgroups of ALL, defined by the t(1;19) and t(9;22) chromosomal translocations (approximately 10% of cases). Polymerase chain reaction (PCR) techniques can identify these clinically important subgroups in the absence of successful cytogenetic studies. PCR analysis also provides a sensitive and specific tool for the detection of minimal residual disease during apparent (clinically defined) remission. Additionally, molecular studies of cases with specific cytogenetic lesions have helped to clarify the events leading to leukemic transformation of normal lymphoid cells. It is reasonable to expect that improved therapeutic strategies will emerge from findings made with molecular diagnostic and treatment monitoring techniques.