Myeloproliferative Neoplasms (MPN)
Myeloproliferative Neoplasms (MPNs) are blood cancers that occur when bone marrow makes too many granulocytes, red blood cells, or platelets. This increase in the number of cells can create problems for blood flow and lead to various symptoms. There are a number of different types of MPN:
• Chronic Myeloid Leukaemia (CML)
• Polycythaemia Vera (PV) - PV occurs when the body makes too many red blood cells
• Essential Thrombocythaemia (ET) - ET occurs when the body makes too many platelets, the part of the blood needed for clotting
• Myelofibrosis (MF) - MF occurs when the bone marrow makes too many blood cells
It is important to classify the type of MPNs as it affects the choice of treatment and efficacy. For patients with MPNs, detection of the BCR/ABL1 fusion helps to differentiate CML from other MPNs, which are largely characterized by mutations in JAK2, CALR, or MPL[2-3].
As mentioned, CML is characterized by BCR/ABL1 fusion gene (also known as Philadelphia chromosome/ translocation) which result from a fusion/ rearrangement between BCR gene on chromosome 22 and ABL1 on chromosome 9. It is important to identify the presence of a BCR/ABL1 fusion in CML as it can be targeted by a Tyrosine Kinase Inhibitor (TKI), such as Imatinib, Nilotinib, Dasatinib, Bosutinib and Ponatinib which are all approved by FDA. Nevertheless, point mutations in ABL1 can confer resistance to ABL1 kinase inhibitors used to treat CML[2-3].
For BCR/ABL1-negative MPNs, three common gene mutations are involved, which are:
The most common mutation among MPNs is the JAK2 V617F mutation. It occurs in exon 14 of JAK2 gene located on chromosome 9. It is present in almost everyone with PV and present in more than 50% of people with ET or MF. Testing for JAK2 V617F is needed for anyone who may have a MPN. A small subset of people with PV may have another JAK2 mutation which occurs in exon 12. If JAK2 V617F mutation is absent, testing for JAK2 exon 12 mutation is indicated[3-4].
CALR & MPL Mutations
CALR & MPL mutations occur in 20-30% and 5-10% of people with ET or MF respectively. If JAK2 V617F mutation is absent, testing for CALR and MPL mutations is indicated in ET and MF.
JAK2, MPL, and CALR mutations are absent in about 10% of people with ET or MF. These are known as triple-negative MPN. Mutation in other genes including ASXL1, EZH2, TET2, IDH1, IDH2, SRSF2, and SF3B1 may help in diagnosis of these cancers[3-4].
Screening for these fusions and mutations is important for disease diagnosis and in delivering personalized cancer care. Oncode MPN panel offers range of PCR and NGS panels to detect mutations and fusions in MPN.
MPN Mutation (DNA Assays)
Table 4: Myeloid 37 genes mutation panel
Table 5: Myeloid 73 genes mutation panel
MPN Fusion (RNA Assays)
Table 6: 87 genes panel
1. Cancer Research UK. (2017). Myeloproliferative Neoplasms. READ MORE
2. National Comprehensive Cancer Network (2017). Myeloproliferative Neoplasms. NCCN Guidelines for Patients. READ MORE
3. Shaver, A. & Jagasia, M. (2016). Molecular Profiling of Chronic Myeloid Leukemia. My Cancer Genome. READ MORE
4. Taylor, J., Xiao, W., & Abdel-Wahab, O. (2017). Diagnosis and Classification of Hematologic Malignancies on the Basis of Genetics. Blood, blood-2017.