Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial d...
Gespeichert in:
| Hauptverfasser: | , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
3 February 2017
|
| In: |
Blood cancer journal
Year: 2017, Jahrgang: 7, Heft: 2 |
| ISSN: | 2044-5385 |
| DOI: | 10.1038/bcj.2017.3 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/bcj.2017.3 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/bcj20173 
|
| Verfasserangaben: | P. Richter-Pechańska, J.B. Kunz, J. Hof, M. Zimmermann, T. Rausch, O.R. Bandapalli, E. Orlova, G. Scapinello, J.C. Sagi, M. Stanulla, M. Schrappe, G. Cario, R. Kirschner-Schwabe, C. Eckert, V. Benes, J.O. Korbel, M.U. Muckenthaler, A.E. Kulozik |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 157590764X | ||
| 003 | DE-627 | ||
| 005 | 20220814152404.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180601s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/bcj.2017.3 |2 doi | |
| 035 | |a (DE-627)157590764X | ||
| 035 | |a (DE-576)50590764X | ||
| 035 | |a (DE-599)BSZ50590764X | ||
| 035 | |a (OCoLC)1341010266 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Richter-Pechańska, Paulina |e VerfasserIn |0 (DE-588)1051778565 |0 (DE-627)786788097 |0 (DE-576)407368949 |4 aut | |
| 245 | 1 | 0 | |a Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia |c P. Richter-Pechańska, J.B. Kunz, J. Hof, M. Zimmermann, T. Rausch, O.R. Bandapalli, E. Orlova, G. Scapinello, J.C. Sagi, M. Stanulla, M. Schrappe, G. Cario, R. Kirschner-Schwabe, C. Eckert, V. Benes, J.O. Korbel, M.U. Muckenthaler, A.E. Kulozik |
| 264 | 1 | |c 3 February 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 01.06.2018 | ||
| 520 | |a In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher’s exact test), inactivation of TP53 (P=0.0007, Fisher’s exact test) and duplication of chr17:q11.2-24.3 (P=0.0068, Fisher’s exact test) in 32/67 of T-ALL relapse samples. Alterations of TP53 were frequently homozygous events, which significantly correlated with higher rates of copy number alterations in other genes compared with wild-type TP53 (P=0.0004, Mann-Whitney’s test). We subsequently focused on mutations with prognostic impact and identified genes governing DNA integrity (TP53, n=8; USP7, n=4; MSH6, n=4), having key roles in the RAS signaling pathway (KRAS, NRAS, n=8), as well as IL7R (n=4) and CNOT3 (n=4) to be exclusively mutated in fatal relapses. These markers recognize 24/49 patients with a second event. In 17 of these patients with mostly refractory relapse and dire need for efficient treatment, we identified candidate targets for personalized therapy with p53 reactivating compounds, MEK inhibitors or JAK/STAT-inhibitors that may be incorporated in future treatment strategies. | ||
| 700 | 1 | |a Kunz, Joachim |d 1974- |e VerfasserIn |0 (DE-588)124297730 |0 (DE-627)085769029 |0 (DE-576)294107703 |4 aut | |
| 700 | 1 | |a Bandapalli, Obul Reddy |d 1977- |e VerfasserIn |0 (DE-588)13397121X |0 (DE-627)559235070 |0 (DE-576)30022544X |4 aut | |
| 700 | 1 | |a Orlova, Elena |e VerfasserIn |0 (DE-588)1160458731 |0 (DE-627)1023638908 |0 (DE-576)505907070 |4 aut | |
| 700 | 1 | |a Korbel, Jan Oliver |d 1975- |e VerfasserIn |0 (DE-588)130346500 |0 (DE-627)499578031 |0 (DE-576)298140969 |4 aut | |
| 700 | 1 | |a Muckenthaler, Martina |e VerfasserIn |0 (DE-588)1046124595 |0 (DE-627)775766496 |0 (DE-576)173146813 |4 aut | |
| 700 | 1 | |a Kulozik, Andreas |d 1959- |e VerfasserIn |0 (DE-588)1025736567 |0 (DE-627)723892032 |0 (DE-576)167091638 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood cancer journal |d [London] : Springer Nature, 2011 |g 7(2017,2) Artikel-Nummer e523, 9 Seiten |h Online-Ressource |w (DE-627)655134174 |w (DE-600)2600560-8 |w (DE-576)339571802 |x 2044-5385 |7 nnas |a Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia |
| 773 | 1 | 8 | |g volume:7 |g year:2017 |g number:2 |a Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/bcj.2017.3 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/bcj20173 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180601 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 1025736567 |a Kulozik, Andreas |m 1025736567:Kulozik, Andreas |d 910000 |d 910500 |e 910000PK1025736567 |e 910500PK1025736567 |k 0/910000/ |k 1/910000/910500/ |p 18 |y j | ||
| 998 | |g 1046124595 |a Muckenthaler, Martina |m 1046124595:Muckenthaler, Martina |d 50000 |d 700000 |d 718000 |e 50000PM1046124595 |e 700000PM1046124595 |e 718000PM1046124595 |k 0/50000/ |k 0/700000/ |k 1/700000/718000/ |p 17 | ||
| 998 | |g 130346500 |a Korbel, Jan Oliver |m 130346500:Korbel, Jan Oliver |d 50000 |e 50000PK130346500 |k 0/50000/ |p 16 | ||
| 998 | |g 1160458731 |a Orlova, Elena |m 1160458731:Orlova, Elena |d 50000 |e 50000PO1160458731 |k 0/50000/ |p 7 | ||
| 998 | |g 13397121X |a Bandapalli, Obul Reddy |m 13397121X:Bandapalli, Obul Reddy |d 50000 |e 50000PB13397121X |k 0/50000/ |p 6 | ||
| 998 | |g 124297730 |a Kunz, Joachim |m 124297730:Kunz, Joachim |d 910000 |d 910500 |e 910000PK124297730 |e 910500PK124297730 |k 0/910000/ |k 1/910000/910500/ |p 2 | ||
| 998 | |g 1051778565 |a Richter-Pechańska, Paulina |m 1051778565:Richter-Pechańska, Paulina |d 910000 |d 910500 |e 910000PR1051778565 |e 910500PR1051778565 |k 0/910000/ |k 1/910000/910500/ |p 1 |x j | ||
| 999 | |a KXP-PPN157590764X |e 3011213267 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.1038/bcj.2017.3"],"eki":["157590764X"]},"note":["Gesehen am 01.06.2018"],"relHost":[{"part":{"volume":"7","issue":"2","text":"7(2017,2) Artikel-Nummer e523, 9 Seiten","year":"2017"},"language":["eng"],"title":[{"title_sort":"Blood cancer journal","title":"Blood cancer journal"}],"pubHistory":["1.2011-"],"note":["Gesehen am 17.07.24"],"disp":"Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemiaBlood cancer journal","physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["655134174"],"zdb":["2600560-8"],"issn":["2044-5385"]},"type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"655134174","origin":[{"publisher":"Springer Nature ; Nature Publ. Group","dateIssuedDisp":"2017-","dateIssuedKey":"2017","publisherPlace":"[London] ; London [u.a.]"}]}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"recId":"157590764X","origin":[{"dateIssuedDisp":"3 February 2017","dateIssuedKey":"2017"}],"person":[{"display":"Richter-Pechańska, Paulina","role":"aut","given":"Paulina","family":"Richter-Pechańska"},{"family":"Kunz","display":"Kunz, Joachim","role":"aut","given":"Joachim"},{"role":"aut","given":"Obul Reddy","display":"Bandapalli, Obul Reddy","family":"Bandapalli"},{"display":"Orlova, Elena","given":"Elena","role":"aut","family":"Orlova"},{"role":"aut","given":"Jan Oliver","display":"Korbel, Jan Oliver","family":"Korbel"},{"given":"Martina","role":"aut","display":"Muckenthaler, Martina","family":"Muckenthaler"},{"given":"Andreas","role":"aut","display":"Kulozik, Andreas","family":"Kulozik"}],"title":[{"title_sort":"Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia","title":"Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia"}],"name":{"displayForm":["P. Richter-Pechańska, J.B. Kunz, J. Hof, M. Zimmermann, T. Rausch, O.R. Bandapalli, E. Orlova, G. Scapinello, J.C. Sagi, M. Stanulla, M. Schrappe, G. Cario, R. Kirschner-Schwabe, C. Eckert, V. Benes, J.O. Korbel, M.U. Muckenthaler, A.E. Kulozik"]},"language":["eng"]} | ||
| SRT | |a RICHTERPECIDENTIFICA3201 | ||