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Unlike ALK-positive ALCL, ALK-negative ALCL tends to occur in older adults (median age at diagnosis: 55–60 years) and presents primarily with lymph node involvement; only 20% of patients with ALK-ALCL present with extra-nodal disease in sites such as the skin, bone, and soft tissues.
Anaplastic lymphoma kinase (ALK) was originally discovered in 1994 [5] [7] in anaplastic large-cell lymphoma (ALCL) cells. ALCL is caused by a (2;5)(p23:q35) chromosomal translocation that generates the fusion protein NPM-ALK, in which the kinase domain of ALK is fused to the amino-terminal part of the nucleophosmin (NPM) protein.
Upregulation of ALK is mainly due to chromosomal translocation t(2;17), resulting in a fusion gene of CLTC with ALK, [4] [7] but can rarely be due to t(2;5), fusing NPM1 with ALK; [2]: 378 the later is the usual finding in anaplastic large cell lymphoma (ALCL).
Anaplastic large cell lymphoma: ALK-positive and ALK-negative types; ... or appropriate care in remission or after cures.
Primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder Peripheral T-cell lymphoma, NOS Angioimmunoblastic T-cell lymphoma Follicular T-cell lymphoma Nodal peripheral T-cell lymphoma with T follicular helper phenotype Anaplastic large cell lymphoma, ALK-positive Anaplastic large cell lymphoma, ALK-negative
Crizotinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) or relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. [ 2 ] [ 3 ] It is also indicated for the treatment of unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive ...
Pfizer's lorlatinib was the first third-generation inhibitor and was approved in 2018 by the US FDA for ALK-positive NSCLC after progression on a first or second-generation inhibitor. Its macrocyclic structure was designed specifically to address some of the most recalcitrant resistance mutations.
ALK-positive anaplastic large cell lymphoma: an aggressive, systemic ALCL that strongly expresses anaplastic lymphoma kinase, i.e. ALK. ALK-negative anaplastic large cell lymphoma: an aggressive, systemic ALCL that does not express ALK. Primary cutaneous anaplastic large cell lymphoma: a less aggressive ALCL that commonly presents as skin tumors.