Professional Documents
Culture Documents
DOI: 10.1002/pbc.26266
Pediatric
Blood &
Cancer
BRIEF REPORT
Magorzata Dawidowska2
Bronisawa Szarzyska-Zawadzka2
Joanna Czerwiska-Rybak3
1 Department of Pediatric Oncology, Hematol-
Magorzata Jarmu-Szymczak2,3
Ludomia Machowska1
Katarzyna Derwich1
Abstract
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1wt , FBXW7wt ,
STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and
a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a ow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by uorescence in situ
hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing
a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set
of remaining molecular alterations. This case documents an unfavorable prognostic potential
of a co-occurrence of this set of molecular genetic events and addresses risk stratication in
T-ALL.
KEYWORDS
INTRODUCTION
CASE PRESENTATION
tional cytogenetic analysis, performed on 12 metaphases, demonstrated 46,XY,t(8;14)(q24;q11)[4]/46,XY[8] karyotype. Interphase uorescence in situ hybridization (FISH) using a Vysis MYC dual-color
wileyonlinelibrary.com/journal/pbc
SKALSKA-SADOWSKA ET AL .
DISCUSSION
The prognostic signicance of molecular genetic abnormalities associated with T-ALL, including those detected in the current case, remains
elusive. We examined outcomes for 28 t(8;14)(q24;q11)-positive TALL cases including 26 children. Eleven of them derived from the only
series of this disease documented so far,1 and the remaining ones
were retrieved from either case reports or research articles published
FIGURE 1
over 5 years).1,5,12,13
technique; and NOTCH1, FBXW7, PTEN, IL7R, FLT3, STAT5B, and WT1
were the only mutations detected (Fig. 2A). After hydration and ras-
buricase reduced uric acid level, the patient was treated accord-
of a sole abnormality.
residual disease load of 2.09% and 0.11% was detected with eight-
SKALSKA-SADOWSKA ET AL .
F I G U R E 2 Multiplex ligation dependent probe amplication (MLPA) analysis of bone marrow cells in T-ALL with t(8;14)(q24;q11.2) in a 4-yearold male. Deletions were dened as a sample/reference ratio <0.7 and are depicted as red dots; (A) at diagnosis and (B) at relapse. The last six
positions, in both panels (A) and (B), are genomic loci localized in X chromosome. The difference in the status of these loci between diagnosis and
relapse is due to the fact that female DNA was used as a reference for the sample at diagnosis (thus mimicking a heterozygous deletion) while male
DNA was used as a reference for the relapse sample
levels.17
clone selection and may indicate relapse from the preleukemic clone.19
SKALSKA-SADOWSKA ET AL .
presentation
contributes
to
scarce
observations
of
t(8;14)(q24;q11) as a candidate T-ALL prognostic factor, and provides an associated molecular prole integrated with known routes
of NOTCH-independent/MYC-mediated leukemogenesis. Prospective
screening for this genetic prole in T-ALL and large-scale clinical trials
are required to fully elucidate its prognostic value.
ACKNOWLEDGMENTS
The authors wish to acknowledge grants 2014/15/B/NZ2/03394 and
2013/11/N/NZ5/03730 to BS-Z from the National Science Centre
Poland. BS-Z was additionally supported by the EMBO short-term fellowship ASTF 502015. Additionally, the authors wish to acknowledge
Dr. . Sdek (Medical University of Silesia) for his contribution to cytometric immunophenotyping and E. Orlova for contribution to MLPA
analysis. We would like to thank Dr. B. Konatkowska who treated the
patient and Professor J. Wachowiak (Pozna University of Medical Sciences) for his strong support.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
REFERENCES
1. Lange BJ, Raimondi SC, Heerema N, et al. Pediatric leukemia/
lymphoma with t(8;14)(q24;q11). Leukemia. 1992;6:613618.
2. Kobos R, Shukla N, Renaud T, Prockop SE, Boulad F, Steinherz PG.
High-dose cyclophosphamide for the treatment of refractory T-cell
acute lymphoblastic leukemia in children. J Pediatr Hematol Oncol.
2014;36:e265e270.
4. Mathieu-Mahul D, Sigaux F, Zhu C, et al. A t(8;14)(q24;q11) translocation in a T-cell leukemia (L1-ALL) with c-myc and TcR-alpha chain locus
rearrangements. Int J Cancer. 1986;38:835840.