@article{
author = "Jurišić, Vladimir and Pavlović, Sonja and Čolović, Nataša and Colović, Milica",
year = "2013",
abstract = "To the editor,
In this letter, we wish to point out the possibility of
transformation of myelofibrosis in acute lymphocytic leukemia without the presence of JAK2V617F mutation.
Myeloproliferative neoplasms (MPN) are hematologic
malignant diseases characterized by a clonal proliferation
of one or several lineages [1]. They represent a phenotypically diverse group of chronic myeloid malignancies
that are characterized by the presence of clonal hematopoiesis and an excessive production of terminally differentiated myeloid blood cells. Typically, they include four
main clinical entities: polycythemia vera (PV), essential
thrombocythemia (ET), primary myelofibrosis (PMF), and
chronic myeloid leukemia (CML). PV, ET, and PMF are
usually subcategorized as bcr-abl-negative MPN. However,
sporadic cases of bcr-abl-positive patients with transformation of primary myelofibrosis were reported but without
JAK2V617F mutation [2].
The prevalence of JAK2V617F mutation [3] differs
between various variants of MF with the higher detection
rate for patients with post-PV MF (91 %) if compared to
PMF (45 %) and post-ET MF (39 %). Some works
emphasize the importance of the predictive role of
JAK2V617F mutation for this transformation. JAK2V617F
mutation is also discussed in myeloproliferative disease and
primary myelofibrosis as well, in respect to clinical prognosis and transformation [4, 5]. The JAK2V617F mutation
was reported to found positive in 7 out of 17 (64 %) analyzed
patients with PMF and with transformation to leukemia. The
risk of transformation to acute leukemia in investigated
patients was around 31 % in JAK-2 positive, but several
studies also indicated possibility of transformation in
JAK-2-negative PMF. However, majority of patients were
transformed to acute myeloid leukemia. We previously
reported possibility of transformation of PMF to acute
lymphocytic leukemia (ALL) [2] and only an additional
case in literature reported transformation of refractory
anemia with ring sideroblasts (RARS) to ALL [4] with
20q- cytogenetic. Patients with PV had also possibility to
transform to PMF, frequently regarding to JAK-2 mutation.
However, no difference in the frequency of transformation
PV patients to acute myeloid leukemia was observed
between the JAK2 positive and JAK2 negative [4].
Here, we want to emphasize the possibility thatPMF can
transform into ALL, probably regarding molecular disturbance in immature hematopoietic precursor cell. Briefly, we
previously reported that patient with 20q- cytogenetic anomaly, which is usually a favorable cytogenetic prognostic factor,
can transform to ALL with Philadelphia-positive finding, but
without JAK2V617F mutation, and with fatal outcome after
10 months [2] pointing out the other factors that can lead to
transformation of PMF into ALL.
Since leukemogenesis is a complex process caused by one
or multiple gene alterations, which perturbs the regulation of
development and maturation of the multipotent hemopoietic
progenitor cells gradually leading to acute leukemia, here we
want to point out that they may have other molecular and
cytogenetic changes except JAK2V617F mutation, which can
be important during transformation. We suggested the continuation of the examination of genetic disturbances in
order to understand a very complex process of transformation
in unstable karyotypes in pre-leukemic conditions",
publisher = "Humana Press Inc, Totowa",
journal = "Medical Oncology",
title = "Possibility of transformation of primary myelofibrosis to ALL without JAK2V617F mutation",
number = "1",
volume = "30",
doi = "10.1007/s12032-012-0398-2"
}
