Acquired resistance to crizotinib in novel CDK14-ALK and CLTC-ALK fusions of ALK-positive large B-cell lymphoma identified by next-generation sequencing.
Cancer Biol Ther
; 24(1): 2271212, 2023 12 31.
Article
em En
| MEDLINE
| ID: mdl-37906510
ABSTRACT
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare subtype of non-Hodgkin lymphoma. ALK inhibitors are being tried to treat recurrent/refractory ALK+ LBCL. A majority of patients with ALK+ tumors respond to crizotinib, but partial cases ultimately develop resistance about a year later. Here, we report a case of ALK+ LBCL carrying a new fusion gene involving CDK14 and ALK, CLTC-ALK gene rearrangements and MTOR gene mutation. The patient had progressive disease after combination of crizotinib and chemotherapy treatment about 5.5 months later, accompanied by reduced abundance of CDK14-ALK, increased abundance of CLTC-ALK and a novel MFHAS1 gene mutation. However, MTOR mutation turned negative. The patient received alectinib combined with hyper-CVAD, then followed by alectinib as monotherapy for 21 months. The patient achieved partial response and remained in a stable condition. This case suggests that CDK14-ALK fusion gene may be more sensitive to crizotinib than CLTC-ALK fusion gene. MTOR is associated with the anti-tumor mechanism of ALK inhibitors. MFHAS1 gene mutation and/or CLTC-ALK gene copy number amplification may involve resistance to crizotinib. Furthermore, alectinib may inhibit the carcinogenicity of these gene changes and improve the prognosis of ALK+ LBCL.
The novel CDK14-ALK fusion gene in ALK+ LBCL was sensitive to crizotinib.MFHAS1 gene mutation and/or CLTC-ALK gene copy number amplification may involve resistance to crizotinib.
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Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
/
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Cancer Biol Ther
Assunto da revista:
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China