To investigate which molecular mast cell phenotypes (as defined by the expressed genes and gene-networks) in bone marrow resident mast cells and their progenitors are associated with the presence or absence of ISM.
ID
Source
Brief title
Condition
- Allergic conditions
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Differences in gene expression and gene-networks in bone marrow resident mast
cells and their progenitors between ISM and non-ISM patients identified by
single-cell RNA sequencing.
Secondary outcome
Differences in gene expression and gene-networks in bone marrow resident mast
cells and their progenitors between clinical subtypes of ISM, as identified by
single-cell RNA sequencing.
Differences in gene expression and gene-networks of other cell types in
unpurified bone marrow aspirate that might be the result of the presence of
mast cells (or their progenitors) carrying the somatic cKIT mutation.
Background summary
Systemic mastocytosis is a disorder characterized by the pathological clonal
proliferation of mast cells as a result of a somatic point mutation of the
proto-oncogene c-KIT.(1,2) Indolent systemic mastocytosis (ISM) is the most
prevalent type.(2) Accumulation and degranulation of mast cells in various
tissues results in a wide clinical spectrum of mast cell activation complaints,
e.g. drowsiness, flushing, typical gastro-intestinal complaints, fatigue. Other
frequent manifestations are osteoporosis and hymenoptera venom allergy
(HVA).(3)
How the c-KIT mutation affects mast cell phenotype unknown, as well as why some
patients mainly show symptoms related to mast cell accumulation and others
mainly to mast cell degranulation. Increased insight in mast cell heterogeneity
between ISM and non-ISM patients will be key to design novel therapeutic
treatment options. Furthermore, the underlying pathophysiology for the
variation in clinical presentation within the ISM population is unknown. We
hypothesize that, as ISM patients show no other bone marrow alterations than
mast cell abundance, clinical differences of subtypes may be traced back to
differences in mast cell (progenitor) phenotypes. Identification of such
differences within the ISM may help us in developing an optimized, personalized
treatment.
Study objective
To investigate which molecular mast cell phenotypes (as defined by the
expressed genes and gene-networks) in bone marrow resident mast cells and their
progenitors are associated with the presence or absence of ISM.
Study design
Single-center, cross-sectional study, using single cell RNA sequencing
(scRNA-seq).
Study burden and risks
This observational study has no specific beneficial health effects for any of
the participating subjects. The performed bone marrow biopsy is part of
standard care. The study requires the withdrawal of an additional sample of
10mL. This entails no additional risks compared to the standard care. This
method of inclusion enables us to include both ISM and non-ISM patients without
the requirement of additional invasive procedures or hospital visits.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
- A clinical suspicion of ISM, based on a constellation of clinical complaints,
including drowsiness, gastro-intestinal complaints, myalgia and fatigue, or
manifestations such as urticaria pigmentosa, osteoporosis or anaphylaxis.
- Eligible for a bone marrow biopsy
- Legally capacitated adults
-The second eligible patient group concerns patient enrolled in the
avapritinib study (research register number 201800849, METc 2018.635). These
patients with a confirmed diagnosis of ISM willl undergo a bone marrow biopsy
as part of the study protocol of the avapritinib study. Therefore, also in this
patient population no additional invasive procedures are required, hence the
additional burden of the current study remains restricted to the withdrawal of
the additional sample.
Exclusion criteria
Lidocaine hypersensitivity.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67451.042.18 |