Quantitative Assessment of Wilms Tumor 1 (WT1) Gene Transcripts in Egyptian Acute Lymphoblastic Leukemia Patients

Abstract

BackgroundAccurate assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients after initial chemotherapy is essential to evaluate the efficacy of therapeutic regimens. Wilms tumor 1 (WT1) is a pan-leukemic marker used for identification of the leukemic clone rather than the use of individual specific molecular aberration of ALL.MethodsUsing a real-time quantitative polymerase chain reaction, bone marrow samples from 41 newly diagnosed Egyptian ALL patients; 22 adults and 19 children were examined for WT1 expression. After induction therapy, WT1 expression was reestimated in 20 ALL patients.Results WT1 was overexpressed in adult and pediatric ALL patients (95.4% and 89.4%, respectively). WT1 expression at diagnosis had no statistically significant impact on disease-free survival of patients (P = 0.054). However, WT1 expression increased after induction chemotherapy in the 3 pediatric patients who had relapse.Conclusions WT1 is a leukemia-associated molecular marker that may be used for the diagnosis and for monitoring clinical progress in ALL; it also can be used as a molecular target for adoptive immunotherapy.

WT1 Overexpression Affecting Clinical Outcome in Non-Hodgkin Lymphomas and Adult Acute Lymphoblastic Leukemia

“…Our findings in B-cell ALL fit in with the results of recent large-scale studies [12][13][14], including the observation that a sudden increase in WT1 expression seems to be associated with an increased risk of relapse. However, our results in ALL represent only a minor contribution to previous reports, since our sample size was relatively small.…”

“…In recent years, some results have been reported in childhood and adult ALL as well. These suggest that while WT1 expression is not a reliable marker of prognosis and minimal residual disease in ALL, WT1 could still become a therapeutic target, as its overexpression was detected in a sufficiently high number of cases [12][13][14]. For the majority of lymphomas, however, no studies have been published to report the possible prognostic significance of WT1 expression, even though a putative role of WT1 in their pathogenesis has been suggested, much like in acute leukemias [15].…”

WT1 overexpression predicted good outcomes in adult B-cell acute lymphoblastic leukemia patients receiving chemotherapy

“…In the current study, we found that the WT1 transcript level at diagnosis was significantly associated with CIR, RFS and OS in adult B-ALL patients who received chemotherapy only and patients without BCR-ABL fusion and KMT2A rearrangements. Although others have studied the prognostic effect of the level of WT1 at diagnosis in patients with ALL, the results have been controversial; some studies reported that high WT1 transcript levels were associated with a good outcome [14,21], while some reported the opposite result [15,17,20], and others revealed no independent prognostic role of WT1 transcript levels for DFS and OS [12,13,16,18]. These studies included diverse populations and were not restricted to adult B-ALL patients, especially those who received chemotherapy only.…”

“…However, whether WT1 transcript levels at the time of diagnosis can predict outcomes in AML patients is still controversial [6][7][8][9][10][11]. The prognostic role of WT1 in ALL is even less clear and more controversial than its role in AML [12][13][14][15][16][17][18][19][20][21]. This indicates that the mechanism of action of WT1 is complex and that WT1 may play the role of an oncogene or a tumor suppressor gene in different tumors or different subgroups of tumors.…”