MPN JAK2 V617F with Sequential Reflex to JAK2 Exon 12-15, CALR, and MPL

Code
NGS-MPJB-03BZ
Panel
Active-Compendium
81270, 81279, 81219, 81339
Clinical
Oncology,Pathology
<p><b>Bone Marrow Aspirate:</b> 1-2 mL in EDTA tube. Sodium Heparin is acceptable.</br>
<b>Peripheral Blood:</b> 3-5 mL in EDTA tube. Sodium Heparin is acceptable.</br>
<b>Note:</b> Test is DNA-based. Please select Extract & Hold - DNA if specimen hold service is desired.</p>
Flag Active
True
Orderable Test Description
<p>This next-generation sequencing (NGS)–based assay is performed as a sequential reflex panel for the evaluation of key driver mutations in myeloproliferative neoplasms (MPN). Testing begins with JAK2 V617F (exon 14) and, if negative, reflexes to JAK2 exons 12–15 , followed by CALR exon 9, and then MPL exon 10. The reflex pathway is discontinued once an informative pathogenic mutation is identified and downstream molecular analyses are not performed; if no mutation is detected, all four targets are reported as negative.</br></br>

Tests may also be ordered individually.</br></br>

<b>Note:</b> This assay replaces the former MPN JAK2 V617F with Sequential Reflex to JAK2 Exon 12-13, CALR, and MPL performed by PCR/fragment analysis/bi-directional sequencing. NY samples are still processed by PCR/fragment analysis/bi-directional sequencing until further notice.</p>
Orderable Turn Around Time
7 Days
Meta Description
This next-generation sequencing (NGS)–based assay is performed as a sequential reflex panel for the evaluation of key driver mutations in myeloproliferative neoplasms (MPN).
Orderable Biomarkers
NY Approved
False
Orderable Biomarkers JSON
{"DNA Sequencing": {"SNVs + Indels": ["CALR", "MPL", "JAK2"]}}
Keywords string
mpn extended, mpn extended reflex, extended reflex, reflex panel, panel, myeloproliferative neoplasms, JAK2 V617F, JAK2, JAK2 Exon 12-14, CALR, calreticulin, MPL MPN JAK2 V617F with Sequential Reflex to JAK2 Exon 12-15, CALR, and MPL
Title URL
mpn-jak2-v617f-with-sequential-reflex-to-jak2-exon-12-15-calr-and-mpl
Clinical Significance

Identification of myeloproliferative neoplasm (MPN)-associated driver mutations is important in the diagnosis, prognosis and therapy selection of BCR-ABL1-negative MPN. JAK2 V617F represents the canonical exon 14 gain-of-function mutation, which has been reported in >95% of patients with polycythemia vera (PV) and approximately 50-60% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). High JAK2 V617F variant allele fraction (>50%) is more commonly observed in PV and is associated with increased risk of myelofibrotic progression in both PV and ET. Targeted therapy directed at the JAK2 V617F mutation is available. A small subset of PV patients that are JAK2 V617F mutation negative will harbor JAK2 mutations in exon 12, usually small in-frame deletions or insertions.

JAK2 exon 12 mutated PV shows similar prognosis to JAK2 V617F mutated cases. Other rare non-V617F mutations can be detected in exons 13, 14 and 15 of the JAK2 gene. Somatic insertions or deletions in exon 9 of CALR gene are detected in 25-35% of patients with ET and PMF. The most common CALR mutations observed include a 52bp deletion (type 1) or 5bp insertion (type 2). PMF patients with mutated CALR have a lower risk of thrombosis and longer overall survival than patients with JAK2 and MPL mutation, however, the association may be limited to those with type 1or type 1-like mutation. Exon 10 MPL mutations, most commonly W515 and S505, are present in approximately 5-10% of patients with PMF and ET. MPL and CALR mutations have been associated with increased risk of MF transformation in ET cases.

(References: PMID: 35767897, 35732831, 36347013, 37357958, 27187622, 29274140, 26473532, and 38269572)

Storage and transportation
Use cold pack for transport, making sure cold pack is not in direct contact with specimen. For fresh samples: refrigerate before shipping and ship same day as drawn whenever possible. Do not freeze.