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. 2014 Oct;99(10):e188-92.
doi: 10.3324/haematol.2014.104992. Epub 2014 Jun 27.

The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse

Obul R Bandapalli  1 , Stephanie Schuessele  1 , Joachim B Kunz  1 , Tobias Rausch  2 , Adrian M Stütz  2 , Noa Tal  3 , Ifat Geron  4 , Nava Gershman  3 , Shai Izraeli  3 , Juliane Eilers  1 , Nina Vaezipour  1 , Renate Kirschner-Schwabe  5 , Jana Hof  6 , Arend von Stackelberg  5 , Martin Schrappe  7 , Martin Stanulla  8 , Martin Zimmermann  9 , Rolf Koehler  10 , Smadar Avigad  11 , Rupert Handgretinger  12 , Viktoras Frismantas  13 , Jean Pierre Bourquin  13 , Beat Bornhauser  13 , Jan O Korbel  14 , Martina U Muckenthaler  15 , Andreas E Kulozik  15
Affiliations

The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse

Obul R Bandapalli et al. Haematologica. 2014 Oct.
No abstract available

Keywords: STAT5B; mutation; pediatric T-ALL.

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Figures

Figure 1.
Figure 1.
STAT5B N642H confers a higher risk of relapse in pediatric T-ALL; (A) Cumulative incidence of relapse (pCIR) and (B) probability of event-free survival (pEFS) for T-ALL patients enrolled in ALL-BFM 2000 with STAT5B wild type (blue) or STAT5B N642H (red). (C) Xenografted cells from Patient 1 at first diagnosis (STAT5B wild type) and at relapse (STAT5B N642H) were harvested from the spleen of leukemic mice, lysed and subjected to SDS-gel electrophoresis and Western blotting. Membranes were probed with anti STAT5B and anti pSTAT5. Tubulin was assessed as a loading control. (D) Expression of downstream STAT5B targets in xenografted leukemia cells: mRNA abundance of the STAT5 downstream targets BCL2, PIM1 and SOCS2 was measured by quantitative RT-PCR in triplicate and set to 1 in STAT5B wild-type cells.
Figure 2.
Figure 2.
STAT5B N642H results in IL3-independent proliferation in BaF3 cells. BaF3-cells were either left untransduced or transduced with either STAT5B wild type or STAT5B N642H. (A) Cells were grown without IL3 and counted on Days 1, 3, 5 and 7. Error bars represent SE from 3 independent experiments. (B) Cells were grown for five days in the presence of increasing concentrations of IL3. Error bars represent SE from 3 independent experiments. (C) BaF3 cells were either harvested after 4 h of cytokine starvation (red), during the steady state phase of growth in medium containing Il-3 (green), or following 4 h of cytokine starvation and subsequent 20 min stimulation with IL3 (10 ng/mL; blue). Cells were fixed, stained for pSTAT5 and analyzed by FACS for STAT5p levels. (D) BaF3 cells were incubated without IL3 for 5 h before IL3 (10ng/mL) was added. After another 20 min, cells were harvested, lysed and subjected to SDS-gel electrophoresis and Western blotting. All samples were analyzed on one gel and blot for STAT5B (upper panel) and pSTAT5 (lower panel). The blots were cut at the indicated positions to excise unrelated tracks. Tubulin was assessed as a loading control. (E) BaF3 cells were transfected with either STAT5B wild type or with STAT5B N642H. Cells were harvested and RNA isolated after 4 h of cytokine deprivation (-IL3) or after a 20 min incubation with IL3 (10 ng/ml) following 4 h cytokine deprivation (+IL3). Expression of the STAT5 target genes BCL2, PIM1 and SOCS2 was quantified by RT-PCR. *P=0.05, **P=0.01, ***P=0.001, ****P=0.0001.
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References

    1. Shochat C, Tal N, Bandapalli OR, Palmi C, Ganmore I, te Kronnie G, et al. Gain-of-function mutations in interleukin-7 receptor-alpha (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med. 2011;208(5):901–8 - PMC - PubMed
    1. Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M, et al. Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet. 2011;43(10):932–9 - PMC - PubMed
    1. De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet. 2013;45(2):186–90 - PMC - PubMed
    1. Kleppe M, Lahortiga I, El Chaar T, De Keersmaecker K, Mentens N, Graux C, et al. Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nat Genet. 2010;42(6):530–5 - PMC - PubMed
    1. Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med. 2008;205(4):751–8 - PMC - PubMed

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