Preliminary data are available about bone
marrow (BM) changes in patients with chronic myeloid
leukemia (CML) who received the molecularly targeted
and highly effective tyrosine kinase inhibitor Imatinib
mesylate (STI571). This review is focused on a
systematic assessment of BM features detectable at
different stages of CML (stable, accelerated, blastic)
following long-term (more than 10 months) treatment.
By applying enzyme- and immunohistochemistry
including monoclonal antibodies visualizing
proliferating cell nuclear antigen (PCNA) and apoptosis
(anti-apostatin), a more elaborate insight into alterations
affecting hematopoiesis and the stroma compartment
was gained. In patients with stable-phase CML therapy
resulted in a significant reduction in cellularity,
neutrophil granulopoiesis and number of
megakaryocytes, accompanied by a retrieval of erythroid
precursors. In patients with Imatinib as the only
treatment morphometric analysis of CD61+
megakaryopoiesis was in keeping with a significant
decrease in maturation defects implying a lesser amount
of atypical micromegakaryocytes almost consistent with
normalization. Moreover, a reduction of the initially
enhanced (CD34+) microvessel density was detectable
associated with a decrease in luminal distension.
Regression of marked to moderate myelofibrosis was
recognizable in about 70% of patients especially in the
accelerated and blastic phases. The amount of myeloblasts, CD34+ progenitor cells and lysozymeexpressing
immature myelomonocytic cells declined
with treatment, but recurred in about 19% of patients
that developed a leukemic relapse after 21±6 months of
therapy. Data on proliferative activity and apoptosis in
general supported in vitro findings concerning the inhibitory effect of this agent on growth associated with
a tendency for stimulated apoptosis, at least in
responding patients