Association of pre-treatment bone marrow morphology and achievement of BCR-ABL1 transcript milestones in CML

Martina Murković; Emina Babarović; Blažen Marijić; Dragana Grohovac; Ita Hadžisejdić

doi:10.1016/j.prp.2023.154517

Association of pre-treatment bone marrow morphology and achievement of BCR-ABL1 transcript milestones in CML

Pathol Res Pract. 2023 Jun:246:154517. doi: 10.1016/j.prp.2023.154517. Epub 2023 May 11.

Authors

Martina Murković¹, Emina Babarović², Blažen Marijić³, Dragana Grohovac⁴, Ita Hadžisejdić⁵

Affiliations

¹ Faculty of Medicine, University of Rijeka, Braće Branchetta 20, Rijeka, Croatia; Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia.
² Faculty of Medicine, University of Rijeka, Braće Branchetta 20, Rijeka, Croatia; Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia; Laboratory for Molecular Pathology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia.
³ Faculty of Medicine, University of Rijeka, Braće Branchetta 20, Rijeka, Croatia; Department of Otorhinolaryngology and Head and Neck Surgery, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia.
⁴ Faculty of Medicine, University of Rijeka, Braće Branchetta 20, Rijeka, Croatia; Department of Internal Medicine, Clinic for Hematology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia.
⁵ Faculty of Medicine, University of Rijeka, Braće Branchetta 20, Rijeka, Croatia; Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia; Laboratory for Molecular Pathology, Clinical Hospital Center Rijeka, Krešimirova 42, Rijeka, Croatia. Electronic address: ita.hadzisejdic@uniri.hr.

PMID: 37182315
DOI: 10.1016/j.prp.2023.154517

Abstract

Chronic myeloid leukemia (CML) is characterized by the fusion gene BCR-ABL1 which encodes aberrantly functioning tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKI) is a landmark of CML management and the main goal is to achieve major molecular response (MMR) which is defined as BCR-ABL1^IS ≤ 0.1 % at 12 months of therapy. The aim of this study is to analyze histologic features of bone marrow (BM) in CML patients at the time of diagnosis and compare it to the level of BCR-ABL1^IS transcript at 3 (BCR-ABL1^IS ≤10 % early molecular response; EMR) and 12 months (MMR) as well as to so called molecularly undetectable leukemia (MUL) to see weather bone marrow morphology can be of value in predicting achievement molecular response milestones. Thirty-two bone marrow biopsies of CML patients, prior TKI therapy, were re-evaluated and CD34 immunohistochemistry was performed to examine microvessel density (MVD) and microvessel area (MVA) and subsequently compared it to the level of BCR-ABL1^IS transcript. This study showed statistically significant association between BM hypercellularity and EMR (p = 0.048) and MUL (p = 0.034), peri-trabecular adipocyte distribution and EMR and MUL (p = 0.027 and p = 0.011, respectively), MMR and bone marrow fibrosis (p = 0.029), loose megakaryocyte clustering and EMR and MUL (p = 0.004 and p = 0.018, respectively), absence of naked nuclei and MUL (p = 0.033) but there was no statistically significant association with vascular parameters. These results suggest that some bone marrow morphologic features prior TKI therapy might be indicators of favorable molecular response.

Keywords: BCR-ABL1; Chronic myeloid leukemia; Major molecular response; Megakaryocyte.

MeSH terms

Antigens, CD34
Bone Marrow*
Fusion Proteins, bcr-abl / genetics
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
Protein Kinase Inhibitors / pharmacology

Substances

Fusion Proteins, bcr-abl
Protein Kinase Inhibitors
Antigens, CD34