engleski

A bone marrow morphometry in prediction of molecular response in chronic myeloid leukemia

Introduction: Chronic myeloid leukaemia (CML) is characterized by the Bcr-Abl genetic translocation which leads to constitutive tyrosine kinase signaling. Treatment with tyrosine kinase inhibitors (TKI) should be monitored in order to define the molecular response (MR) which correlate with the quantity of BCR-ABL transcript levels and number of CML cells, respectively. To date, only clinical and laboratory data have been used in predicting MR leaving aside the information given by the tumor itself in the bone marrow at the time of diagnosis to which the therapy has being administered. The aim of the study is to analyze the standard patohistological parameters in bone marrow biopsy of the patients with CML and to compare to MR status. Materials and Methods: Thirty-two bone marrow biopsy cases were examined using H&E and standard histochemistry staining after standard formalin fixation and mild decalcification procedure under the light microscope. Additional immunohistochemical staining using anti-CD34 antibody (clone….) was performed and computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm2 (MVD) and the percentage of microvessel area in total section area (TVA). The MR status was defined as positive if ⩽0.1% BCR-ABL mRNA transcripts were detected in peripheral patient's blood... Results: Among 26 patients with positive MR status the bone marrow morphometric characteristics were: overall hypercellularity of bone marrow (p=0.037), diffuse distribution of multiplied megakaryocytes (p=0.041), non-compact megakaryocyte clusters (p=0.007) and cloud-like megakaryocyte nuclei (p=0.027). Other morphologic parameters like myelofibrosis, erythrocyte content and morphology, megakaryocyte distribution, megakaryocyte nuclear lobulation, staghorn nuclei, naked and dysmorphic nuclei were not in statistically significant association with MR status. Blood vessel morphometry determined by MVD and TVA showed no connection to MR status as well. Conclusions: Our results are showing that some, mainly megakaryocyte, morphologic characteristics could serve as predictors of MR in patients on TKI inhibitors at the time of CML diagnosis before given therapy that could be modified perhaps according to the bone marrow biopsy status.

Chronic myeloid leukaemia ; Molecular response ; Morphology

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