NPM-ALK fusion

Taken together, our findings validate CD70 as a promising target for TCL treatment using CAR NK cells. Our approach provides a solid foundation for the clinical translation of CD70-targeting CAR NK-cell therapy for patients with TCL.

A cell-based evaluation of this predicted ALK protein variant revealed activation of downstream targets-STAT3, AKT and ERK- and ALK inhibitors, crizotinib or lorlatinib, treatment inhibited the growth of xenograft tumors with stable TENM3-ALK expression. We determined whether TENM3-ALK affects transformation and proliferation using a soft agar colony formation assay. As expected, the cells that expressed an empty vector and wild type ALK line did not produce a considerable number of colonies, whereas TENM3-ALK transfected cells showed anchorage-independent growth, resulting in the production of a higher number of colonies .The evidence for the role of ALK receptor signaling in stimulating neuroblastoma tumor cell growth and the demonstrated in vitro and in vivo efficacy of the ALK selective inhibitors in this study provide biological and clinical justification for the further exploration of this combination and testing in patients with recurrent or refractory neuroblastoma.

Out data demonstrated that treatment-free remission was durable for more than two years in ALK-positive ALCL patients following the cessation of ALK TKIs. MRD-guideddiscontinuation decision may be considered for ALK-positive ALCL patients treated with ALK inhibitors who had undetectable MRD.Table 1. Summary of patient characteristics and outcomes of ALK TKI discontinuationNo.SexAge at diagnosisAnn Arbor stageALK TKILines of prior therapyTreatment duration of ALK TKI (months)Reason for cessationDuration of ALK TKI cessation (months)Best response to ALK TKITime of MRD assessment after TKI cessationMRD after TKI cessation1M22IIBCrizotinib393.9Fertility27.8CR5.6Negative2F20IVBCrizotinib190.9Fertility25.9CR0.0Negative3M23IVCeritinib142.7Adverse event61.9CR61.9Negative4F58IVCrizotinib31.7Cost86.6CR72.1Negative5F64IVBCrizotinib113.6Cost31.0CR14.4Negative6M75IVCrizotinib211.7Cost80.2CR62.0Negative

Arm CZ of ANHL12P1 demonstrated that the addition of CZ to standard treatment prevented relapses during therapy for children with ALCL, MDD predicted EFS, and the addition of CZ resulted in unexpected thromboembolic events. Overall survival and EFS rates are consistent with the highest reported outcomes for children with ALCL.

Our findings suggest that 3'ALK MDD assessments will be beneficial for patients with ALK-positive ALCL, because 3'ALK MDD can be assessed without confirming ALK fusion partners by karyotyping of the lymphoma tissue. Stratification of patients with ALK-positive ALCL based on MDD using dPCR can be beneficial for the establishment of new standard treatments.