LPL deletion is associated with poorer response to ibrutinib-based treatments and overall survival in TP53 -deleted chro
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ORIGINAL ARTICLE
LPL deletion is associated with poorer response to ibrutinib-based treatments and overall survival in TP53-deleted chronic lymphocytic leukemia Wei Liu 1 & Jan A. Burger 2 & Jie Xu 1 & Zhenya Tang 1 & Gokce Toruner 1 & Mahsa Khanlari 1 & L. Jeffrey Medeiros 1 & Guilin Tang 1 Received: 13 May 2020 / Accepted: 14 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Ibrutinib-based therapy represents a recent success in managing high-risk CLL patients with 17p/TP53 deletion. However, a subset of CLL patients are resistant to therapy. Deletion of lipoprotein lipase (LPL) has been postulated as a potential evasion mechanism to ibrutinib-based therapy. In this study, we assessed for LPL deletion by fluorescence in situ hybridization in 176 consecutive CLL patients with 17p/TP53 deletion. LPL deletion was detected in 35 (20%) of CLL patients. Patients with LPL deletion (del) showed a higher frequency of CD38 expression but have comparable frequencies of somatic hypermutation and ZAP-70 expression compared with patients with normal (nml) LPL. Gene mutation analysis showed that TP53 was mutated in 68% of LPL-del versus 91% of LPL-nml patients. The overall response to ibrutinib-based therapy was 57%, including 37% complete remission (CR) and 20% partial remission (PR) in patients with LPL-del versus 90% (56% CR and 34% PR) in patients with LPL-nml (p < 0.001). LPL-del patients also showed a poorer overall survival (OS) compared with patients with LPL-nml (median OS, 236 months versus undefined, p < 0.001). In summary, the data presented establish an association between LPL deletion, resistance to ibrutinibbased therapy, and poorer overall survival in TP53-deleted CLL patients. We suggest that LPL deletion might be utilized as a biomarker for risk stratification and to predict therapeutic response in this high-risk group of CLL patients. Keywords Lipoprotein lipase (LPL) . Chronic lymphocytic leukemia (CLL) . Ibrutinib . TP53
Introduction Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries, and patients have extremely heterogeneous clinical courses [1]. To predict the prognosis of CLL patients, there are two well-accepted staging systems, the modified Rai [2] and Binet [3] systems, which are based on simple physical Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04223-y) contains supplementary material, which is available to authorized users. * Guilin Tang [email protected] 1
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA
2
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
examination and standard laboratory tests. More recently, genetic and chromosomal aberrations have been integrated in multiple models to better stratify CLL patients for prediction of therapeutic response and prognosis [1, 4, 5]. The tumor-suppressor gene TP53, located on chromo
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