Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with <italic>MYD88</italic>-Mutated Chronic Lymphocytic Leukemia in Taiwan.

<bold><italic>Introduction:</italic></bold> Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia. <bold><italic>Methods:</italic></bold> Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities. <bold><italic>Results:</italic></bold> Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including <italic>IGLL5</italic>, <italic>MYD88</italic>, <italic>TCHH</italic>, <italic>DSCAM</italic>, <italic>AXDND1</italic>, <italic>BICRA</italic>, <italic>KMT2D</italic>, <italic>MYT1L</italic>, and <italic>RBM43</italic>, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts. <italic>IGLL5</italic>, <italic>MYD88</italic>, and <italic>KMT2D</italic> genes were further analyzed by targeted sequencing in another 185 CLL patients, unraveling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of <italic>MYD88</italic> was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). <italic>MYD88</italic> mutations were significantly associated with <italic>IGLL5</italic> mutations (<italic>p</italic> = 0.0004), mutated <italic>IGHV</italic> (<italic>p</italic> < 0.0001) and 13q deletion (<italic>p</italic> = 0.0164). CLL patients with co-occurrence of <italic>MYD88</italic> mutations with <italic>KMT2D</italic> or/and <italic>IGLL5</italic> mutations were associated with a significantly inferior survival compared to those with <italic>MYD88</italic> mutation alone (not reached vs. 131.8 months, <italic>p</italic> = 0.007). In multivariate analysis, <italic>MYD88</italic> mutation without <italic>KMT2D</italic> or <italic>IGLL5</italic> mutations was an independently favorable predictor. <bold><italic>Conclusions:</italic></bold> <italic>IGLL5</italic>, <italic>MYD88</italic>, and <italic>KMT2D</italic> mutations were enriched in Taiwanese CLL, and co-occurrence of <italic>MYD88</italic> mutations with <italic>KMT2D</italic> or/and <italic>IGLL5</italic> mutations was associated with a poorer prognosis. [ABSTRACT FROM AUTHOR]