ERG DELETION EXERTS A CD2-DEPENDENT POSITIVE PROGNOSTIC IMPACT ON IKZF1-DELETED CHILDHOOD ALL

Konference: 2013 18th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Molecular Markers in acute lymphoblastic leukemia

Číslo abstraktu: S538

Autoři: MUDr. Markéta Kubričanová-Žaliová, Ph.D.; MUDr. Olga Zimmermannová; Petra Dörge, PhD; Dr. Cornelia Eckert, PhD; MD Anja Möricke; Martin Zimmermann, Ph.D.; Mgr. Jan Stuchlý; Andrea Teigler-Schlegel, PhD; Dr. phil. nat. Rolf Koehler, PhD; Prof. MD Claus R. Bartram; Dr. Leonid Karawajew, p; Peter Rhein; MD Gunnar Cario; Doc. MUDr. Jan Zuna, Ph.D.; MD Martin Schrappe; MD Martin Stanulla, MSc

Background:

B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) is a clinically and biologically heterogeneous disease. Based on the presence of routinely screened recurrent genetic aberrations, most cases can be classified into genetically defined subgroups. Despite this success, a still significant proportion of patients falls into the so-called “B-other” category with largely unknown genetic background and heterogeneous outcome. Importantly, the majority of relapses occur within patients who lack any known strong prognostic feature. To improve the prognosis of this group, identification of new and more accurate risk predictors is of ongoing interest.

Aims:

Using SNP microarray analysis, intragenic deletions of the ERG gene on chromosome 21q22.3 (ERGdel) were recently described as a recurrent abnormality in childhood ALL. However, detailed characterization of this aberration in the context of large modern clinical trials has not been performed so far. In our study we aimed to assess the incidence of ERGdel in childhood ALL and to evaluate its clinical value as a prognostic marker.

Methods:

We developed a multiplex PCR assay to screen ERGdel on the genomic level and screened 1323 patients treated on the multicentre ALL-BFM 2000 protocol. A commercially available multiplex ligation-dependent probe amplification (MLPA) kit was used to analyze IKZF1 deletions. Other clinical and laboratory parameters were acquired by routine diagnostic procedures.

Results:

We identified 60 cases with ERGdel, all exclusively within BCP-ALL. The majority of positive patients were observed in the “B-other” subgroup (44/403). Interestingly, in at least 1/3 of cases the deletion was bi-/oligoclonal and it was significantly associated with higher age, CD2-positivity and IKZF1 deletion. We found no or only weak associations of ERGdel alone with prognosis. However, when combined with CD2 status, the CD2-positive/ERGdel patients demonstrated superior outcome. This effect was significant even within cases harbouring IKZF1 deletions which have previously been shown to have a negative prognostic impact in the ALL-BFM 2000 trial population. In addition, we analyzed stability of ERGdel between diagnosis and relapse in all six CD2-negative/ERGdel relapses. In 3/6 cases the ERG deletions were lost and in the remaining 3 cases the relapse deletions differed from those found at diagnosis.

Summary and Conclusions:

To conclude, we describe a high incidence of ERGdel in B-other ALL. Our data suggest that the ERG locus is specifically prone to deletion in this subgroup. Nevertheless, the deletion does not seem to play a driving role in the pathogenesis of the disease. We show that combined with CD2-positivity the ERGdel confers a superior prognosis which even overcomes the negative impact of concurrent IKZF1 deletions.

Support: P302/12/G101; UNCE204012

Abstrakta v časopise Haematologica 2013, Suppl1

Online Program

Datum přednesení příspěvku: 15. 6. 2013