Publications by authors named "Daniel J Zinn"

6 Publications

  • Page 1 of 1

Thalidomide, A Rational Agent for Treatment of Multicentric Reticulohistiocytosis.

Dermatol Case Rep 2019 8;4(1). Epub 2019 Apr 8.

Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas, USA.

A patient with Multifocal Reticulohistiocytosis (MRH) of skin and joints failed treatment with etanercept, methotrexate, hydroxychloroquine, prednisone, bisphosphonates and hydroxyzine. Long term treatment with thalidomide led to marked improvement in joint and cutaneous manifestations.
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http://dx.doi.org/10.35248/2684-124X.19.4.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289025PMC
April 2019

Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma.

Oncotarget 2017 Jul;8(28):46065-46070

Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX 77030, USA.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor. These data highlight the importance of identifying specific MAPK pathway alterations as part of the diagnostic workup for patients with histiocytic disorders rather than initiating empiric treatment with MEK inhibitors.
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http://dx.doi.org/10.18632/oncotarget.17521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542249PMC
July 2017

Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis.

Blood 2016 11 11;128(21):2533-2537. Epub 2016 Oct 11.

Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.

Langerhans cell histiocytosis (LCH) is characterized by inflammatory lesions containing pathologic CD207 dendritic cells with constitutively activated ERK. Mutually exclusive somatic mutations in MAPK pathway genes have been identified in ∼75% of LCH cases, including recurrent BRAF-V600E and MAP2K1 mutations. To elucidate mechanisms of ERK activation in the remaining 25% of patients, we performed whole-exome sequencing (WES, n = 6), targeted BRAF sequencing (n = 19), and/or whole-transcriptome sequencing (RNA-seq, n = 6) on 24 LCH patient samples lacking BRAF-V600E or MAP2K1 mutations. WES and BRAF sequencing identified in-frame BRAF deletions in the β3-αC loop in 6 lesions. RNA-seq revealed one case with an in-frame FAM73A-BRAF fusion lacking the BRAF autoinhibitory regulatory domain but retaining an intact kinase domain. High levels of phospho-ERK were detected in vitro in cells overexpressing either BRAF fusion or deletion constructs and ex vivo in CD207 cells from lesions. ERK activation was resistant to BRAF-V600E inhibition, but responsive to both a second-generation BRAF inhibitor and a MEK inhibitor. These results support an emerging model of universal ERK-activating genetic alterations driving pathogenesis in LCH. A personalized approach in which patient-specific alterations are identified may be necessary to maximize benefit from targeted therapies for patients with LCH.
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http://dx.doi.org/10.1182/blood-2016-08-733790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123197PMC
November 2016

Hydroxyurea: a new old therapy for Langerhans cell histiocytosis.

Blood 2016 11 29;128(20):2462-2465. Epub 2016 Sep 29.

Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1182/blood-2016-06-721993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114488PMC
November 2016

Langerhans Cell Histiocytosis: Emerging Insights and Clinical Implications.

Oncology (Williston Park) 2016 Feb;30(2):122-32, 139

Langerhans cell histiocytosis is a disorder characterized by lesions that include CD207+ dendritic cells along with an inflammatory infiltrate. Langerhans cell histiocytosis has a highly variable clinical presentation, ranging from a single lesion to potentially fatal disseminated disease. The uncertainty as to whether Langerhans cell histiocytosis is a reactive or a neoplastic disease has resulted in a long-standing debate on this question, and the limited understanding of the pathogenesis of the disease has impeded clinical improvement for patients. The current standard of care for multisystem Langerhans cell histiocytosis, empirically derived chemotherapy with vinblastine and prednisone, cures fewer than 50% of patients, and optimal therapies for relapse and neurodegenerative disease remain uncertain. Recent research advances support a model in which Langerhans cell histiocytosis arises due to pathologic activation of the mitogen-activated protein kinase (MAPK) pathway in myeloid precursors. Redefinition of Langerhans cell histiocytosis as a myeloid neoplastic disorder driven by hyperactive ERK supports the potential of chemotherapy with efficacy against immature myeloid cells, as well as mutation-specific targeted therapy.
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February 2016