North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies

Shah, Urvi A.; Chung, Elaine Y.; Giricz, Orsi; Pradhan, Kith; Kataoka, Keisuke; Gordon-Mitchell, Shanisha; Bhagat, Tushar D.; Mai, Yun; Wei, Yongqiang; Ishida, Elise; Choudhary, Gaurav S.; Joseph, Ancy; Rice, Ronald E.; Gitego, Nadege; Parrish, Crystall; Bartenstein, Matthias; Goel, Swati; Mantzaris, Ioannis; Shastri, Aditi; Derman, Olga; Binder, Adam; Gritsman, Kira; Kornblum, Noah; Braunschweig, Ira; Bhagat, Chirag; Hall, Jeff; Graber, Armin; Ratner, Lee; Wang, Yanhua; Ogawa, Seishi; Verma, Amit; Ye, B. Hilda; Janakiram, Murali

doi:10.1182/blood-2018-01-824607

Cited by 65 publications

(95 citation statements)

References 42 publications

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“…This is consistent with the survival reported by others and us in a predominantly African American cohort . The worse outcomes for NHBs may be related to a delay in diagnosis or differences in genetic characteristics …”

Section: Discussionsupporting

confidence: 92%

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Epidemiology and survival trend of adult T‐cell leukemia/lymphoma in the United States

Shah

Qiao

et al. 2019

Cancer

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Background Globally, 5 million to 10 million people are infected with human T‐cell leukemia virus type 1, which causes adult T‐cell leukemia/lymphoma (ATLL) in 2% to 5% of the carriers. ATLL is a rare but extremely aggressive malignancy that can be challenging to diagnose. Very little data exist on the incidence patterns of ATLL in the United States. Methods ATLL cases reported to the National Program of Cancer Registries, the Surveillance, Epidemiology, and End Results (SEER) program, and the New York State Cancer Registry were used for the study. Age‐adjusted incidence rates were calculated by age, race/ethnicity, sex, and year of diagnosis. The 5‐year survival rate was compared among race/ethnicity groups with the SEER data. Results During 2001‐2015, 2148 ATLL cases were diagnosed in the United States, 18% of which were in New York State. New York State had the highest incidence rate for ATLL, with a rising trend especially among non‐Hispanic blacks (NHBs), whereas the incidence was stable across the remainder of the United States. NHBs were diagnosed at a younger median age (54 years) and had a shorter overall survival (6 months). In New York City, only 22.6% of the ATLL cases diagnosed were born in North America. Conclusions This is the largest epidemiological study of ATLL in the United States and shows a rising incidence in New York City. NHBs have a younger age at presentation and poor overall survival. The rising incidence is largely due to NHBs originating from the Caribbean.

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Section: Discussionsupporting

confidence: 92%

“…HTLV‐1 is also prevalent at low levels in the United States . Within the United States, New York and Florida contain the majority of ATLL cases because of the higher number of Caribbean immigrants in these areas …”

Section: Introductionmentioning

confidence: 99%

Epidemiology and survival trend of adult T‐cell leukemia/lymphoma in the United States

Shah

Qiao

et al. 2019

Cancer

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“…We have shown that differences in disease biology are possible between Japanese and North American variants, and hence genomic profiling to understand differences could be valuable. 3 In a recent study, CCR4 gain-of-function mutations were observed in 32.8% of 116 patients from Japan and were found to be prognostic of treatment response with a 5-year overall survival difference of 80% in the group with CCR4 gain-of-function mutations versus 24.7% in the group without these mutations. 4 In a group of 53 predominantly North American patients with ATLL, 14 (26%) had a CCR4 gain-of-function mutation.…”

Section: Identifying Potential Factors Of Variable Response To Mogamumentioning

confidence: 99%

Identifying potential factors of variable response to mogamulizumab in adult T-cell leukemia/lymphoma between Japanese and other populations

Janakiram

Miljković

2019

Haematologica

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“…The contribution of epigenetic dysregulation to the pathogenesis of MTCL is further supported by many lines of genetic data demonstrating several recurring mutations in genes governing a host of epigenetic functions, including DNMT3A, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300. [13][14][15][16][17][18] Collectively, the data suggest that there may be "epigenetic vulnerabilities" that can be exploited in a rational therapeutic approach. Mutations in several genes involved in DNA methylation, namely, IDH2, TET2, and DNMT3, were reported in separate publications in 2012.…”

Section: Molecular Pathogenesismentioning

confidence: 99%

The rapidly changing landscape in mature T‐cell lymphoma (MTCL) biology and management

Marchi

O’Connor

2019

CA A Cancer J Clinicians

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Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.

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North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies

Abstract: Key Points North American ATLL has a distinct genomic landscape with a high frequency of prognostic epigenetic mutations, including EP300 mutations. ATLL samples with mutated EP300 have compromised p53 function and are selectively sensitive to decitabine treatment.

Cited by 65 publications

References 42 publications

Epidemiology and survival trend of adult T‐cell leukemia/lymphoma in the United States

Epidemiology and survival trend of adult T‐cell leukemia/lymphoma in the United States

Identifying potential factors of variable response to mogamulizumab in adult T-cell leukemia/lymphoma between Japanese and other populations

The rapidly changing landscape in mature T‐cell lymphoma (MTCL) biology and management

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