Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis: Alternative drivers in anaplastic large cell lymphoma

Fabrizio Tabbò, Maurilio Ponzoni, Raul Rabadan, Francesco Bertoni, Giorgio Inghirami

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose of Review: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFκB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.

Original languageEnglish
Pages (from-to)374-381
Number of pages8
JournalCurrent Opinion in Hematology
Volume20
Issue number4
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Anaplastic Large-Cell Lymphoma
anaplastic lymphoma kinase
Anthracyclines
Therapeutics
Pediatrics
Drug Therapy

Keywords

  • Anaplastic lymphoma kinase
  • Kinase inhibitors
  • Lymphoid differentiation
  • Mouse models
  • Signalling pathways

ASJC Scopus subject areas

  • Hematology

Cite this

Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis : Alternative drivers in anaplastic large cell lymphoma. / Tabbò, Fabrizio; Ponzoni, Maurilio; Rabadan, Raul; Bertoni, Francesco; Inghirami, Giorgio.

In: Current Opinion in Hematology, Vol. 20, No. 4, 07.2013, p. 374-381.

Research output: Contribution to journalArticle

Tabbò, Fabrizio ; Ponzoni, Maurilio ; Rabadan, Raul ; Bertoni, Francesco ; Inghirami, Giorgio. / Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis : Alternative drivers in anaplastic large cell lymphoma. In: Current Opinion in Hematology. 2013 ; Vol. 20, No. 4. pp. 374-381.
@article{3e66e03fc7024969a7cad6dcb15ecf1a,
title = "Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis: Alternative drivers in anaplastic large cell lymphoma",
abstract = "Purpose of Review: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFκB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.",
keywords = "Anaplastic lymphoma kinase, Kinase inhibitors, Lymphoid differentiation, Mouse models, Signalling pathways",
author = "Fabrizio Tabb{\`o} and Maurilio Ponzoni and Raul Rabadan and Francesco Bertoni and Giorgio Inghirami",
year = "2013",
month = "7",
doi = "10.1097/MOH.0b013e3283623c07",
language = "English",
volume = "20",
pages = "374--381",
journal = "Current Opinion in Hematology",
issn = "1065-6251",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis

T2 - Alternative drivers in anaplastic large cell lymphoma

AU - Tabbò, Fabrizio

AU - Ponzoni, Maurilio

AU - Rabadan, Raul

AU - Bertoni, Francesco

AU - Inghirami, Giorgio

PY - 2013/7

Y1 - 2013/7

N2 - Purpose of Review: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFκB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.

AB - Purpose of Review: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFκB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.

KW - Anaplastic lymphoma kinase

KW - Kinase inhibitors

KW - Lymphoid differentiation

KW - Mouse models

KW - Signalling pathways

UR - http://www.scopus.com/inward/record.url?scp=84880223497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880223497&partnerID=8YFLogxK

U2 - 10.1097/MOH.0b013e3283623c07

DO - 10.1097/MOH.0b013e3283623c07

M3 - Article

C2 - 23673339

AN - SCOPUS:84880223497

VL - 20

SP - 374

EP - 381

JO - Current Opinion in Hematology

JF - Current Opinion in Hematology

SN - 1065-6251

IS - 4

ER -