Clinical significance of microcytosis in patients with primary myelofibrosis

Abstract

Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia (p=0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis.

Prognostic implications of low transferrin saturation in patients with primary myelofibrosis

“…They found that although microcytosis was relatively frequent (28% and 24% of untreated patients), it had no association with overall survival. It was also reported that microcytosis showed significant association with low TSAT, both univariately and after adjustment for other correlated factors, but had no association with anemia [17]. Our results are in line with these findings.…”

“…This phenomenon could be due to extramedullary hematopoiesis in the spleen that dominates iron uptake, and thus restrains iron supply to the bone marrow [26]. Due to aforementioned problems, some authors proposed low TSAT as a parameter of choice to evaluate iron deficiency in PMF [17]. Low TSAT could be a consequence of absolute or functional iron deficiency, but this is challenging to discriminate.…”

“…Nevertheless, TSAT affected quality of erythropoiesis, as observed by decrease in MCV associated with lower TSAT values. Two author groups previously investigated properties of microcytosis in a population of PMF patients [17,18]. They found that although microcytosis was relatively frequent (28% and 24% of untreated patients), it had no association with overall survival.…”

“…This phenomenon of iron deprivation results in ironrestricted erythropoiesis and usually manifests with development or worsening of pre-existing anemia. Low TSAT, microcytosis and anemia are relatively frequent findings among myelofibrosis patients [17,18]. Clinical and prognostic significance of low TSAT have not been investigated in this population so far.…”

Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents

“…JAK2 has been reported to play an important role in hepcidin-dependent FPN1 degradation, a mechanism by which JAK2 activity may contribute to the development of ACD by mediating iron restriction within the reticuloendothelial system and functional iron-deficient anemia 23. Interestingly, although not fully understood, anemia in patients with MF shows typical signs of ACD 16,17,31. Therefore, we speculated whether MMB exerts its positive anemia effects via a JAK2-dependent pathway on FPN1 degradation and whether MMB may also ameliorate anemia in an inflammation-driven rat model of ACD.…”