Treatment resistance in chronic lymphocytic leukemia : the role of the p53 pathway
The importance of studying p53 pathway defects in chronic lymphocytic leukemia (CLL) has been promoted by the demonstration of the fundamentally different clinical course of patients with 17p deletion. The observation of resistance to chemotherapy and mutation of the remaining TP53 allele explain the clinical presentation of CLL with 17p deletion. Here we review recent evidence that cases with TP53 mutation in the absence of the deletion of 17p have a similar clinical and biological course as cases carrying the deletion 17p. In addition, other principal components of the DNA damage pathway reportedly are de-regulated by mutation (ATM), deletion (ATM) or potentially more complex down-regulation (miR-34a) in CLL. Nonetheless, challenges remain because we can only explain resistance in a proportion of the cases that are resistant to first line treatment. This is of particular practical interest because our armamentarium of drugs in clinical use that acts independent of the DNA damage pathway is growing, for example antibody-based treatment (alemtuzumab), immuno-modulating drugs (lenalidomide), CDK inhibitors (flavopiridol) and steroids.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2009 |
---|---|
Erschienen: |
2009 |
Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
---|---|
Enthalten in: |
Leukemia & lymphoma - 50(2009), 3 vom: 01. März, Seite 510-3 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Zenz, Thorsten [VerfasserIn] |
---|
Links: |
---|
Themen: |
Journal Article |
---|
Anmerkungen: |
Date Completed 17.08.2009 Date Revised 16.01.2019 published: Print Citation Status MEDLINE |
---|
doi: |
10.1080/10428190902763533 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM187656290 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM187656290 | ||
003 | DE-627 | ||
005 | 20231223180451.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231223s2009 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1080/10428190902763533 |2 doi | |
028 | 5 | 2 | |a pubmed24n0626.xml |
035 | |a (DE-627)NLM187656290 | ||
035 | |a (NLM)19347737 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Zenz, Thorsten |e verfasserin |4 aut | |
245 | 1 | 0 | |a Treatment resistance in chronic lymphocytic leukemia |b the role of the p53 pathway |
264 | 1 | |c 2009 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 17.08.2009 | ||
500 | |a Date Revised 16.01.2019 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a The importance of studying p53 pathway defects in chronic lymphocytic leukemia (CLL) has been promoted by the demonstration of the fundamentally different clinical course of patients with 17p deletion. The observation of resistance to chemotherapy and mutation of the remaining TP53 allele explain the clinical presentation of CLL with 17p deletion. Here we review recent evidence that cases with TP53 mutation in the absence of the deletion of 17p have a similar clinical and biological course as cases carrying the deletion 17p. In addition, other principal components of the DNA damage pathway reportedly are de-regulated by mutation (ATM), deletion (ATM) or potentially more complex down-regulation (miR-34a) in CLL. Nonetheless, challenges remain because we can only explain resistance in a proportion of the cases that are resistant to first line treatment. This is of particular practical interest because our armamentarium of drugs in clinical use that acts independent of the DNA damage pathway is growing, for example antibody-based treatment (alemtuzumab), immuno-modulating drugs (lenalidomide), CDK inhibitors (flavopiridol) and steroids | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Review | |
650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
700 | 1 | |a Mohr, Julia |e verfasserin |4 aut | |
700 | 1 | |a Edelmann, Jennifer |e verfasserin |4 aut | |
700 | 1 | |a Sarno, Antonio |e verfasserin |4 aut | |
700 | 1 | |a Hoth, Patrick |e verfasserin |4 aut | |
700 | 1 | |a Heuberger, Maria |e verfasserin |4 aut | |
700 | 1 | |a Helfrich, Hanne |e verfasserin |4 aut | |
700 | 1 | |a Mertens, Daniel |e verfasserin |4 aut | |
700 | 1 | |a Dohner, Hartmut |e verfasserin |4 aut | |
700 | 1 | |a Stilgenbauer, Stephan |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Leukemia & lymphoma |d 1989 |g 50(2009), 3 vom: 01. März, Seite 510-3 |w (DE-627)NLM012624047 |x 1029-2403 |7 nnns |
773 | 1 | 8 | |g volume:50 |g year:2009 |g number:3 |g day:01 |g month:03 |g pages:510-3 |
856 | 4 | 0 | |u http://dx.doi.org/10.1080/10428190902763533 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 50 |j 2009 |e 3 |b 01 |c 03 |h 510-3 |