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Article ; Online: Male Invasive Lobular Breast Cancer: Clinicopathologic Features Including Recurrence Score Results From a Population-Based Database.

Balatico, Michael / Ruano, Ana L / Cleary, Allison S / Lomo, Lesley / Gulbahce, H Evin

Archives of pathology & laboratory medicine

2024 Volume 148, Issue 3, Page(s) 263–264

MeSH term(s)	Male ; Humans ; Breast Neoplasms/pathology ; Carcinoma, Lobular/pathology ; Carcinoma, Ductal, Breast/pathology
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2023-0364-LE
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Article ; Online: Genome editing-induced t(4;11) chromosomal translocations model B cell precursor acute lymphoblastic leukemias with KMT2A-AFF1 fusion.

Pan, Feng / Sarno, Jolanda / Jeong, Johan / Yang, Xin / Jager, Astraea / Gruber, Tanja A / Davis, Kara L / Cleary, Michael L

The Journal of clinical investigation

2024 Volume 134, Issue 1

Abstract: A t(4;11) leukemia model established from CRISPR-engineered chromosomal translocations between the KMT2A and AFF1 genes recapitulate proteomic, epigenomic, and transcriptomic features of primary patient leukemias. ...

Abstract	A t(4;11) leukemia model established from CRISPR-engineered chromosomal translocations between the KMT2A and AFF1 genes recapitulate proteomic, epigenomic, and transcriptomic features of primary patient leukemias.
MeSH term(s)	Humans ; Translocation, Genetic ; Gene Editing ; Proteomics ; Myeloid-Lymphoid Leukemia Protein/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; DNA-Binding Proteins/genetics ; Transcriptional Elongation Factors/genetics
Chemical Substances	Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; AFF1 protein, human (150826-18-9) ; DNA-Binding Proteins ; Transcriptional Elongation Factors
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI171030
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Article ; Online: ASO Visual Abstract: Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with De Novo Pancreatic Adenocarcinoma.

Fogliati, Alessandro / Zironda, Andrea / Fiorentini, Guido / Adjei, Stella / Amro, Abdelrahman / Starlinger, Patrick P / Grotz, Travis E / Warner, Susanne G / Smoot, Rory L / Thiels, Cornelius A / Kendrick, Michael L / Cleary, Sean P / Truty, Mark J

Annals of surgical oncology

2024

Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-15016-2
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Article ; Online: Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells.

Pan, Feng / Iwasaki, Masayuki / Wu, Wenqi / Jiang, Yanan / Yang, Xin / Zhu, Li / Zhao, Zhigang / Cleary, Michael L

Blood advances

2023 Volume 7, Issue 11, Page(s) 2504–2519

Abstract: Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangement (MLLr) comprises a cellular hierarchy in which a subpopulation of cells serves as functional leukemia stem cells (LSCs). They are maintained by a unique gene expression ... ...

Abstract	Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangement (MLLr) comprises a cellular hierarchy in which a subpopulation of cells serves as functional leukemia stem cells (LSCs). They are maintained by a unique gene expression program and chromatin states, which are thought to reflect the actions of enhancers. Here, we delineate the active enhancer landscape and observe pervasive enhancer malfunction in LSCs. Reconstruction of regulatory networks revealed a master set of hematopoietic transcription factors. We show that EP300 is an essential transcriptional coregulator for maintaining LSC oncogenic potential because it controls essential gene expression through modulation of H3K27 acetylation and assessments of transcription factor dependencies. Moreover, the EP300 inhibitor A-485 affects LSC growth by targeting enhancer activity via histone acetyltransferase domain inhibition. Together, these data implicate a perturbed MLLr-specific enhancer accessibility landscape, suggesting the possibility for disruption of the LSC enhancer regulatory axis as a promising therapeutic strategy in AML.
MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Chromatin ; Gene Expression Regulation ; Oncogenes ; Stem Cells/metabolism
Chemical Substances	Chromatin
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008787
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Article ; Online: Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

Gudmundsdottir, Hallbera / Fogliati, Alessandro / Grotz, Travis E / Thiels, Cornelius A / Warner, Susanne G / Smoot, Rory L / Truty, Mark J / Kendrick, Michael L / Nagorney, David M / Halfdanarson, Thorvardur R / Cleary, Sean P / Starlinger, Patrick

Annals of surgical oncology

2024

Abstract: Background: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of ... ...

Abstract	Background: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. Methods: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. Results: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). Conclusions: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.
Language	English
Publishing date	2024-04-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-15316-7
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Article ; Online: Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with de Novo Pancreatic Adenocarcinoma.

Annals of surgical oncology

2024 Volume 31, Issue 4, Page(s) 2632–2639

Abstract: Background: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly ... ...

Abstract	Background: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. Methods: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). Results: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. Conclusions: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.
MeSH term(s)	Humans ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/surgery ; Adenocarcinoma/pathology ; Neoadjuvant Therapy ; Pancreatic Intraductal Neoplasms ; Adenocarcinoma, Mucinous/drug therapy ; Adenocarcinoma, Mucinous/surgery ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/surgery ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/surgery ; Adenocarcinoma, Papillary/pathology ; Retrospective Studies
Language	English
Publishing date	2024-02-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-14875-5
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Article ; Online: Gender-Affirming Mastectomy: Psychosocial and Surgical Outcomes in Transgender Adults.

Bertrand, A A / DeLong, Michael R / McCleary, Sean P / Nahabet, Edward H / Slack, Ginger C / DaLio, Andrew L / Weimer, Amy K / Kwan, Lorna / Bernacki, Jessica / Rudkin, George H

Journal of the American College of Surgeons

2024 Volume 238, Issue 5, Page(s) 890–899

Abstract: Background: Limited literature exists examining the effects of gender-affirming mastectomy on transmasculine and nonbinary patients that is prospective and uses validated survey instruments.: Study design: The psychosocial functioning of ... ...

Abstract	Background: Limited literature exists examining the effects of gender-affirming mastectomy on transmasculine and nonbinary patients that is prospective and uses validated survey instruments. Study design: The psychosocial functioning of transmasculine and nonbinary patients was compared between patients who underwent gender-affirming mastectomy and those who had not yet undergone surgery. Participants were enrolled in a single-site, combined study of surgical and psychosocial outcomes, including a cross-sectional cohort of preoperative and postoperative patients, as well as separate prospective cohort. Participants completed the BREAST-Q psychosocial and sexual well-being modules, the BODY-Q satisfaction with chest and nipples modules, the Body Image Quality of Life Inventory, the Transgender Congruence Scale, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7 scale before and after surgery. We also examined how patient demographic factors correlated with postoperative surgical and psychosocial outcomes. Results: A total of 111 transmasculine and nonbinary patients 18 to 63 years of age (mean ± SD 26.5 ± 8) underwent mastectomy and were included in the study. All were included in the cross-sectional cohort, and 20 were enrolled in the prospective cohort. More than one-third (34.2%) of patients were nonbinary. After surgery, psychosocial and sexual well-being, satisfaction, body image-related quality of life, and gender congruence were increased (p < 0.001) in both cohorts, and depression (p < 0.009 cross-sectional), and anxiety (p < 0.001 cross-sectional) were decreased. The most common adverse event was hypertrophic scarring, which occurred in 41 (36.9%) participants. Conclusions: In this study of transmasculine and nonbinary adults, gender-affirming mastectomy was followed by substantial improvements in psychosocial functioning.
MeSH term(s)	Adult ; Humans ; Female ; Transgender Persons/psychology ; Mastectomy/methods ; Prospective Studies ; Quality of Life ; Cross-Sectional Studies ; Breast Neoplasms/surgery ; Treatment Outcome
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1181115-8
ISSN	1879-1190 ; 1072-7515
ISSN (online)	1879-1190
ISSN	1072-7515
DOI	10.1097/XCS.0000000000000940
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Article ; Online: Age and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B-cell precursor populations.

Atre, Tanmaya / Farrokhi, Ali / Jo, Sumin / Salitra, Samuel / Duque-Afonso, Jesus / Cleary, Michael L / Rolf, Nina / Reid, Gregor S D

Blood advances

2023 Volume 7, Issue 22, Page(s) 7087–7099

Abstract: Common infections have long been proposed to play a role in the development of pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, epidemiologic studies report contradictory effects of infection exposure on subsequent B-ALL risk, and no ... ...

Abstract	Common infections have long been proposed to play a role in the development of pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, epidemiologic studies report contradictory effects of infection exposure on subsequent B-ALL risk, and no specific pathogen has been definitively linked to the disease. A unifying mechanism to explain the divergent outcomes could inform disease prevention strategies. We previously reported that the pattern recognition receptor (PRR) ligand Poly(I:C) exerted effects on B-ALL cells that were distinct from those observed with other nucleic acid-based PRR ligands. Here, using multiple double-stranded RNA (dsRNA) moieties, we show that the overall outcome of exposure to Poly(I:C) reflects the balance of opposing responses induced by its ligation to endosomal and cytoplasmic receptors. This PRR response biology is shared between mouse and human B-ALL and can increase leukemia-initiating cell burden in vivo during the preleukemia phase of B-ALL, primarily through tumor necrosis factor α signaling. The age of the responding immune system further influences the impact of dsRNA exposure on B-ALL cells in both mouse and human settings. Overall, our study demonstrates that potentially proleukemic and antileukemic effects can each be generated by the stimulation of pathogen recognition pathways and indicates a mechanistic explanation for the contrasting epidemiologic associations reported for infection exposure and B-ALL.
MeSH term(s)	Mice ; Humans ; Animals ; Child ; Ligands ; Signal Transduction ; RNA, Double-Stranded/pharmacology ; B-Lymphocytes ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Chemical Substances	Ligands ; RNA, Double-Stranded
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010782
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Article ; Online: Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Gudmundsdottir, Hallbera / Yonkus, Jennifer A / Thiels, Cornelius A / Warner, Susanne G / Cleary, Sean P / Kendrick, Michael L / Truty, Mark J / Grotz, Travis E

Annals of surgical oncology

2023 Volume 30, Issue 12, Page(s) 7833–7839

Abstract: Background: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy ...

Abstract	Background: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. Patients and methods: Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. Results: In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. Conclusions: CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-14138-3
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Article: Functional Characterization of Transforming Growth Factor-β Signaling in Dasatinib Resistance and Pre-BCR

Mostufi-Zadeh-Haghighi, Gila / Veratti, Pia / Zodel, Kyra / Greve, Gabriele / Waterhouse, Miguel / Zeiser, Robert / Cleary, Michael L / Lübbert, Michael / Duque-Afonso, Jesús

Cancers

2023 Volume 15, Issue 17

Abstract: The multi-kinase inhibitor dasatinib has been implicated to be effective in pre-B-cell receptor (pre-BCR)-positive acute lymphoblastic leukemia (ALL) expressing the E2A-PBX1 fusion oncoprotein. The TGFβ signaling pathway is involved in a wide variety of ... ...

Abstract	The multi-kinase inhibitor dasatinib has been implicated to be effective in pre-B-cell receptor (pre-BCR)-positive acute lymphoblastic leukemia (ALL) expressing the E2A-PBX1 fusion oncoprotein. The TGFβ signaling pathway is involved in a wide variety of cellular processes, including embryonic development and cell homeostasis, and it can have dual roles in cancer: suppressing tumor growth at early stages and mediating tumor progression at later stages. In this study, we identified the upregulation of the TGFβ signaling pathway in our previously generated human dasatinib-resistant pre-BCR
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15174328
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