ABL1 F359V

First-line therapy was available for 16 pts and was imatinib for 11 pts, nilotinib for 2 pts, dasatinib for 3 pts. Our data confirmed the efficacy of ponatinib in second or later lines of treatment. All pts, including those treated for resistance, achieved optimal responses at 3 mos. We also showed that TFR may be feasible for some pts treated in second or subsequent lines, not only for intolerance.

A technology of DNA-based NGS alternative to standard RNA-based approaches has shown promising results inKD ABL1 mutations detection, with results highly matching to SS or RNA-based NGS detection. The method is reproducible and can be easily implemented in the laboratory routines. The advantages of the technology are evident in the conditions of limited access to RNA-based NGS or other restrictions (costs, long distance/ time transportation, DNA based laboratory sample collections for retrospective analysis).

Integrated genomic sequencing combined with RNA-sequencing can successfully discover and confirm a wide range of variants, from SNVs to CNVs. This strategy may be an effective method for identifying actionable findings and understanding the pathophysiological mechanisms underlying MBC-CML, as well as providing further insights into the genetic basis of MBC-CML and its management in the future.

CMs or polyclonal mutation analysis is particularly crucial for severe patients who have received multiple consecutive TKIs treatments, and those with multiple Background: mutations and a higher risk of progression to clinical resistance. Our results showed that the inhouse designed NGS-based screening protocols could decipher TKIs resistant mutations more comprehensively than SS(Fig 1), and worthy of being implicated in clinical practice.

Nilotinib (NIL) 600 mg daily has demonstrated its superiority over Imatinib 400 mg daily in terms of response and incidence of deep molecular response in the front-line chronic phase (CP) CML setting...NIL first-line efficiently limits progression of newly diagnosed CP-CML patients and provides high rates of sustained MR4.5, allowing TFR in a substantial proportion of pts. However, the onset of arterial occlusive events, especially in the elderly is a matter of concern in the choice of this compound at treatment initiation.