We conclude that besides morphology of megakaryocytes and other features, JAK2V617F allelic burden can help differentiate CMML from PMF with monocytosis.
Chronic myelomonocytic leukemia (CMML) is a clinically heterogeneous neoplasm in which JAK2 inhibition has demonstrated reductions in inflammatory cytokines and promising clinical activity.
Of note, 2 cases of JAK2 V617F+ primary myelofibrosis with SRSF2 mutation initially were diagnosed as CMML based on significant peripheral blood monocytosis.
JAK2V617F mutation was detected after transformation to CMML in 1 of them; in the other, a novel translocation t(5;12)(p13;q24) was observed at the time of progression to acute leukemia.
All bone marrow biopsies of JAK2(V617F)-mutated CMML showed increased erythropoiesis, a marked myeloid and megakaryocytic hyperplasia with occasionally clustered megakaryocytes, and a mild or moderate (grade 1 or 2) fibrosis; six cases showed an increased number of dilated sinusoids and reactive lymphoid nodules.
To study the prevalence of the Val617PheJAK2 mutation in familial cases of myeloproliferative disorder (MPD) and its possible implication as a predisposing genetic factor, we analyzed 72 families including 174 patients (81 polycythemia vera [PV], 68 essential thrombocythemia [ET], 11 myelofibrosis with myeloid metaplasia [MMM], 12 chronic myeloid leukemia), 1 systemic mastocytosis, and 1 chronic myelomonocytic leukemia (CMML).
Interestingly, one of the patients with SM and the patient with CNL with JAK2V617F had a history of lymphoma, and this patient with SM also had associated myelofibrosis and CMML.