Persistence of TEL‐AML1 transcript in acute lymphoblastic leukemia in long‐term remission

Abstract

Background : It has recently been shown that t (12;21) (p13;q 22) is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). We have analyzed this translocation in an attempt to evaluate its incidence and to monitor minimal residual disease (MRD) with t (12; 21) rearrangement by detection of TEL-AML1 transcript in patients with childhood ALL. Procedure : All cryopreserved bone marrow samples were analyzed using a nested reverse transcriptionpolymerase chain reaction (RT-PCR) method. TEL-AML1 transcripts were searched for in 34 ALL patients, including six in relapse consecutively diagnosed at our institution between 1991 and 1997. Results : TEL-AML1 transcripts were found in five (19%) of 27 patients with B precursor ALL. The patients with BCR-ABL , chromosome 11q23 rearrangement and T-ALL patients did not express TEL-AML1 transcripts. Moreover, MRD in five patients with TEL-AML1 transcripts were analyzed in serial samples. Although TEL-AML1 transcripts disappeared soon after the beginning of chemotherapy in three of the five patients, one patient continued to express them for up to 21 months without recurrence and remained in continuous complete remission for seven years after the cessation of chemotherapy. The remaining patient was admitted to our hospital after the second relapse but died following a failure to induce complete remission. Conclusion : For most patients, the presence of TEL-AML1 transcripts suggests excellent chemosensitivity and a favorable prognosis, but some patients with these transcripts have a different outcome. The present study suggests the possibility that a persistence of MRD is not necessarily related to a relapse of ALL with TEL-AML1 fusion. The prognostic significance of TEL-AML1 transcript remains controversial. Further studies are needed to evaluate the relation between the TEL-AML1 transcript and prognosis.

Outcome of ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia in the NOPHO‐ALL‐1992 protocol: frequent late relapses but good overall survival

“…Furthermore, frequent late relapses and similar incidences of the ETV6/RUNX1 transcript in ALLs at diagnosis and relapse have been noted by some (Nakao et al , 1996; Harbott et al , 1997; Seeger et al , 1998, 1999; Tsang et al , 2001) but not by other authors (Loh et al , 1998; Rubnitz et al , 1999; Zuna et al , 1999). The fact that the ETV6/RUNX1 fusion may persist for a long time after cessation of chemotherapy without heralding relapse and that the relapses occasionally are derived from an ETV6/RUNX1 ‐positive clone other than the one present at diagnosis, as evidenced by different ETV6 deletions and IGH/TCR rearrangements at diagnosis and relapse, strongly suggests that some late ‘relapses’ originate in lingering preleukaemic t(12;21)‐positive clones, a finding which may explain why a sustained second remission often can be achieved and which should be taken into account in treatment decisions (Ford et al , 2001; Endo et al , 2003; Konrad et al , 2003; Peham et al , 2004; Zuna et al , 2004; Metzler et al , 2006).…”

The Neoplasms of Precursor Lymphoblasts

“…Hyperdiploidy is reported in up to 50% of children with precursor B-ALL [2] , but it is far less frequent in adult patients. Th e most common chromosomal additions include chromosomes 21 (often multiple copies), 4, 6, 10, 14, 17, 18, 20, X, and duplication of 1q and isochromosome 17q [51,52] . Hyperdiploidy indicates favorable prognosis, particularly in association with trisomy of chromosomes 4, 6, and 10 [2,51,52] .…”

A unique complex translocation involving six different chromosomes in a case of childhood acute lymphoblastic leukemia with the Philadelphia chromosome and adverse prognosis

“…It is likely that the observed clinical heterogeneity reflects a diverse pathogenesis of leukemia. The molecular basis of childhood ALL is to a large extent unknown, and it is likely that significant advances in the treatment of this malignancy are dependent on a better understanding of the molecular events that cause the disease (1,2). A number of investigators have attempted to identify groups of genes, termed ʻtranscriptional signaturesʼ whose expression can be directly associated with drug resistance (3).…”