Molecular Mechanisms and Diagnosis of Mastocytosis

Investigation of Cellular and Molecular Pathologic Mechanisms in Mast Cell Disorders.

Mastocytosis is a disorder characterized by presence of excessive numbers of mast cells in skin, bone marrow and internal organs. It can affect both children and adults, males and females and individuals from all ethnic backgrounds, although precise demographic information about the affected populations is not available as it is a rare disorder. Mastocytosis in children is generally limited to the skin and follows a self limited course, while it is a disorder of the hematopoietic stem cell associated with somatic mutations of the c-kit gene in most patients with adult-onset of disease. There is no known curative therapy for most patients with systemic mastocytosis. Recent research studies identified several subtypes of disease with distinct clinical and pathologic features, however, a precise understanding of the incidence as well as molecular pathology of different disease subtypes is lacking. This study aims to examine molecular and cellular pathological aspects of disease in patients with mastocytosis and correlate findings with clinical presentation and prognosis. Patients will undergo a routine history and physical examination, and diagnostic tests will be ordered as dictated by each patient's clinical presentation. Blood and bone marrow will be obtained for diagnostic and research purposes. Genetic analysis of the c-kit gene regulating mast cell growth and differentiation will be performed. It is hoped that findings obtained from this study will help to design novel therapies for mastocytosis and other disorders in which mast cells play a critical role.

Study Overview

• Status: Completed
• Conditions: Mastocytosis
• Intervention / Treatment: Other: Collection of blood and bone marrow

• Study Type: Observational
• Enrollment (Actual): 136

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with confirmed or suspected mast cell disease

Description

Inclusion Criteria:

• Confirmed or suspected diagnosis of mastocytosis.
• Ability to give informed consent (by the patient or legal guardian if minor)

Exclusion Criteria:

• Inability or not willing to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants evaluated for mastocytosis; Observational study of all patients referred for suspected mast cell disease. Collection of blood or bone marrow for analysis during diagnostic procedures.	Other: Collection of blood and bone marrow; 5-8 cc blood or bone marrow was additionally collected for analysis during diagnostic procedures. No assigned interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of the patients with clonal and non-clonal mast cell disorders	Patients were categorized into one of the clonal and non-clonal mast cell disorder categories after availability of diagnostic data	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of KIT D816V mutation in blood, bone marrow and sorted mast cells	KIT D816V mutation was assessed in patient samples containing various proportions of neoplastic mast cells.	1 week

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Cem Akin, M.D., Ph.D., University of Michigan

Publications and helpful links

General Publications

• Akin C. Clonality and molecular pathogenesis of mastocytosis. Acta Haematol. 2005;114(1):61-9. doi: 10.1159/000085563.
• Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91. doi: 10.1182/blood-2005-10-3969. Epub 2006 Jan 24.
• Akin C, Metcalfe DD. Systemic mastocytosis. Annu Rev Med. 2004;55:419-32. doi: 10.1146/annurev.med.55.091902.103822.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 9, 2006
• First Posted (Estimate): June 12, 2006

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Mutation; Mast cell disease; Anaphylaxis; c-kit; Mastocytosis (suspected or proven)
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Hypersensitivity; Neoplasms, Connective Tissue; Immune Complex Diseases; Mastocytosis
• Other Study ID Numbers: 2004-0246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO