MPN comprise a group of distinct entities with overlapping pathogenetic mechanisms, clinical and histologic features, and molecular mutational profiles. Despite their similarities, they exhibit important differences in disease course and overall survival.
May evolve into, myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), although the myeloproliferative diseases, on the whole, have a much better prognosis than these conditions
In 1951, William Dameshek described the concept of ‘myeloproliferative disorders (MPDs)‘ by grouping together chronic myelogenous leukaemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and erythroleukemia; he reasoned that a self-perpetuating trilineage myeloproliferation underlined their pathogenesis. Pre-Dameshek luminaries who laid the foundation for this unifying concept include Bennett, Virchow, Heuck, Vaquez, Osler, Di Guglielmo and Epstein. In 1960, Nowell and Hungerford discovered the Philadelphia (Ph) chromosome in CML. In 1967, Fialkow and colleagues used X-linked polymorphisms to establish CML as a clonal stem cell disease. Also in 1967, the PV Study Group was summoned by Louis Wasserman to study the natural history of PV and conduct large-scale clinical trials. In 1972, Janet Rowley deciphered the Ph chromosome as a reciprocal translocation between chromosomes 9 and 22, thus paving the way for its subsequent characterization as an oncogenic BCR-ABL mutation. In 1996, Brian Druker discovered imatinib-a small molecule ABL inhibitor with exceptional therapeutic activity in CML. In 2005, a gain-of-function JAK2 mutation (JAK2V617F) was described in BCR-ABL-negative MPDs, raising the prospect of a CML-like treatment strategy in PV, ET and PMF. The current review considers these and other landmark events in the history of MPDs.
Hematopoietic pluripotent stem cells have self-renewal capability and give rise to either myeloid or the lymphoid lineage which further differentiates into various mature blood cells such as red blood cells (RBC), lymphocytes, granulocytes, megakaryocytes, and macrophages. The hematopoietic process is determined by the bone marrow environment, growth factors, and transcription factors.
World Health Organization (WHO) classification:
Depending on the presence or absence of BCR-ABL1 fusion gene
Phenotypic driver mutations:
The cardinal and mutually exclusive mutations in MPNs occur in JAK2, CALR, or MPL, referred to herein as the “phenotypic drivers” because of their role in driving the myeloproliferative phenotype. All of these converge on JAK-STAT signaling
Classical (BCR-ABL1-negative) MPNs::
The diagnosis of MPNs is often challenging due to similarities in the pathogenesis and symptoms of MF, PV, and ET. The diagnosis is typically made by a hematologist who will generally order blood and molecular tests, as well as a bone marrow biopsy.
World Health Organization (WHO) 2016 criteria:
WHO diagnostic criteria for the classical MPNs were established to facilitate differential diagnosis in clinical practice