Eligibility

Inclusion criteria for the registry are:

a) Patients investigated for a myeloproliferative phenotype: unexplained Hct>0.48 (F) or >0.52 (M) or platelet count >450 x 10^9/L

AND

b) Finding on myeloid gene panel of either uncommon acquired or germline variants in myeloproliferative driver genes or acquired variants in non-MPN driver genes, i.e. one of the following:

(i)      Acquired variant(s) in MPN driver gene (JAK2/MPL), which is not at a known hotspots (i.e. outside JAK2 V617F and MPL 515/505). Variants may be annotated as VUS (variant of uncertain significance), likely pathogenic or pathogenic by the reporting laboratory.

(ii)    Likely germline variant(s)* in JAK2, MPL or SH2B3 with low frequency in population databases, which are considered of potential relevance to the clinical phenotype. Variants may be annotated as VUS, likely pathogenic or pathogenic by the reporting laboratory. Most germline variants with a frequency >0.1% in population databases do not warrant submission, unless there is a strong suspicion that in spite of this frequency, the variant is relevant in the individual case.

(iii)   Variants in genes other than the standard MPN phenotypic drivers which appear likely acquired (including genes involved in clonal haematopoiesis), present without MPN drivers and in the absence of an alternative confirmed myeloid disorder such as MDS or MDS/MPN. Variants should be annotated as likely pathogenic or pathogenic by the reporting laboratory and present without MPN driver gene hotspot variants.

*Laboratories may use their own criteria and judgement in considering that a variant is likely to be germline, but most would have variant allele frequency (VAF) 40-60% (most often 45-55%).

Order of priority for case collection:

1. Cases with a myeloproliferative phenotype but no other MPN driver hotspot variant;

2. Cases falling into categories (i) and (ii) above, with both a myeloproliferative phenotype and a co-existing canonical MPN driver variant (i.e. JAK2 V617F or MPL 515/505).

Cases with a non-hotspot variant in a "MPN gene" (e.g. MPL) but without a clear myeloproliferative phenotype (i.e. thrombocytosis, erythrocytosis) are not required.