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MPN panel

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This is the present diagnostic panel for myeloproliferative neoplasms


Purpose

To identify key driver mutations associated with BCR-ABL1 negative MPNs


Sample and turn-around time

The MPN assay is most sensitive when performed on a 10ml EDTA blood less than 48 hours old. It will detect the mutation if it is present in 5% of cells.

The primary test performed is for JAK2 V617F. Analysis of further components will be performed on request. The turn-around time for this test depends on the mutation detected but will be less than 10 days in most cases.


Component genetic tests

1. JAK2 V617F mutation analysis

2. JAK2 exon 12 mutation analysis

3. CALR mutation analysis

4. MPL mutation analysis


Background

Each mutation affects signalling of the JAK2 pathway which is downstream of important cytokine receptors critical for myeloid cell formation. Mutation of JAK2 causes abnormal signal activity affecting pathways downstream of receptors for EPO, G-CSF and TPO; JAK2 mutation therefore drives abnormal cell proliferation and may result in the disorders PV, ET or PMF. Mutation of MPL or CALR affect only signaling from the TPO receptor so result only in the disorders ET or PMF. The precise phenotype depends on additional mutations of further genes.


Occurrence

JAK2 V617F
PV 95%; ET 50-60%; PMF 50-60%
JAK2 exon 12
PRV 3%; ET 0%; PMF 0%
CALR
PRV 0%; ET 20-25%; PMF 20-25%
MPL
PRV 0%; ET 2-3%; PMF 3-5%


Additional notes:

1. Cases negative for mutation of these genes PV 2%, ET 10-15%, PMF 10-15%

2. Reported incidence of JAK2 V617F in phenotypically normal older individuals 0.5%

3. Estimated incidence of JAK2 V617F in phenotypically normal individuals with unusual thrombosis (splanchnic or non-splanchnic) 3-5%


Bibilography: http://www.bloodjournal.org/content/129/6/667