当前位置： SCI文献检索 > LEUKEMIA期刊下所有文献 > Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.

Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.

Abstract：

:Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance.

journal_name

Leukemia

journal_title

Leukemia

authors

Branford S,Kim DDH,Apperley JF,Eide CA,Mustjoki S,Ong ST,Nteliopoulos G,Ernst T,Chuah C,Gambacorti-Passerini C,Mauro MJ,Druker BJ,Kim DW,Mahon FX,Cortes J,Radich JP,Hochhaus A,Hughes TP,International CML Foundation Ge

doi

10.1038/s41375-019-0512-y

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

1835-1850

issue

eissn

0887-6924

issn

1476-5551

pii

10.1038/s41375-019-0512-y

journal_volume

pub_type

杂志文章,评审

在线工具

Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.