Blood, 1 March 2003, Vol. 101, No. 5, pp. 1665-1665
Closing the gap for detection of residual
posttransplantation leukemia?
The detection of minimal residual disease (MRD) after
allogeneic hematopoietic stem cell transplantation (HSCT) by molecular methods has become an important diagnostic tool for clinical
decision-making with regard to posttransplantation immunomodulatory
measures, such as the withdrawal of immunosuppression or
adoptive infusions of donor lymphocytes. The high efficacy of early
interventions directed against residual molecular and cytogenetic
disease after allogeneic HSCT is best documented for imminent
relapses of chronic myelogenous leukemia as demonstrated by the
induction of complete and durable cytogenetic, as well as
molecular, responses in patients with residual cells bearing the
bcr-abl gene rearrangement and its chimeric
transcripts. Indeed, the success of adoptive cellular immunotherapy
of MRD after allogeneic HSCT currently represents some of the
most convincing clinical evidence supporting the concept of
cellular immunotherapy of human cancer.
The Wilms tumor suppressor gene (WT1) encodes a
zinc-finger transcriptional factor that can modulate the expression of
several genes coding for growth factors and their receptors. Transient expression of WT1 has been detected in small fractions
of uncommitted and lineage-committed hematopoietic progenitor cells,
but the functional role of WT1 in the development and
regulation of the normal hematopoiesis is currently not well
characterized. Further, constitutive expression of wild-type or mutant
WT1 has been demonstrated in a variety of hematologic
malignancies and, particularly, in blasts of nearly all acute leukemias
irrespective of lineage-specificity. Therefore, WT1
expression may be regarded as a nonspecific "panleukemic" molecular
marker, and quantitative monitoring of WT1 transcripts holds
promise to become a universal tool for the evaluation of MRD after
chemotherapy or HSCT, especially for the approximately 50% of acute
leukemias without an established disease-specific gene rearrangement.
This expectation is further promoted by the work of Ogawa and coworkers
(page 1698), which strongly supports that sequential analyses of
WT1 transcript expression levels in marrow cells after allogeneic HSCT can be used to reliably predict leukemic relapse and
responses to immunomodulatory interventions against imminent or overt
posttransplantation relapse. If confirmed by larger prospective studies, this work would substantially contribute to close the diagnostic gap of MRD detection and to define universal MRD thresholds for clinical decision-making after HSCT.
Dietrich W. Beelen
University of Essen,
Germany
