International Journal of Hematology and Oncology
2023, Vol 33, Num 4 Page(s): 248-257
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The Potential Role of CAL2 and EZH2 Immunohistochemical Stainings as Diagnostic and Prognostic Surrogate Markers in Classical BCR/ABL1-negative Myeloproliferative Neoplasms
Ece OZOGUL1, Müfide OKAY OZGEYIK2, Arzu SAGLAM AYHAN1, Umit YAVUZ MALKAN3, Ibrahim Celalettin HAZNEDAROGLU3, Aysegul UNER1
1Hacettepe University Faculty of Medicine, Department of Pathology
2Saglik Bilimleri University, Hamidiye Faculty of Medicine, Eskisehir Health and Research Center, Department of Hematology
3Hacettepe University Faculty of Medicine, Department of Hematology
Keywords: Myeloproliferative neoplasms, EZH2, CAL2, Immunohistochemistry
Classical BCR/ABL-1-negative myeloproliferative neoplasms (MPN) are hematopoietic stem cell disorders characterized by clonal proliferation of more than one mature myeloid cell lineage. The most common etiology is the constitutive activation of the JAK/STAT signalling pathway, caused by three main driver mutations: JAK2V617F, CALR, and MPL. In this study, we analyzed the distribution of these driver mutations in our series of classical BCR/AB1-negative MPN patients and their correlation with clinical symptoms, bone marrow, and laboratory findings. We also explored the efficacy of using the CAL2 antibody to identify CALR mutations and studied the potential of using EZH2 antibody expression levels as a prognostic indicator. Our study of 78 BCR/ABL1-negative MPN patients found JAK2V617 mutation in 57.7%, CALR mutation in 11.5%, and MPL mutation in 1.3% of cases. Thrombosis was the most common initial symptom, observed in 25% of patients, predominantly in those with JAK2V617F mutation (p= 0.02). CAL2 was positive in nearly all megakaryocytes of CALR mutant cases (7/9). EZH2 H-scores in egakaryocytes were lower in patients with a higher reticulin fibrosis score (p= 0.013), and thrombotic events were more frequently observed in these patients (p= 0.081). Our findings suggest that CAL2 and EZH2 immunohistochemical staining have potential as diagnostic and prognostic surrogate markers for MPN. Nevertheless, presently, the most crucial components in the diagnosis and prognosis of MPN are comprehensive molecular profiling and its alignment with other diagnostic tools.
Ece OZOGUL1, Müfide OKAY OZGEYIK2, Arzu SAGLAM AYHAN1, Umit YAVUZ MALKAN3, Ibrahim Celalettin HAZNEDAROGLU3, Aysegul UNER1
1Hacettepe University Faculty of Medicine, Department of Pathology
2Saglik Bilimleri University, Hamidiye Faculty of Medicine, Eskisehir Health and Research Center, Department of Hematology
3Hacettepe University Faculty of Medicine, Department of Hematology
Keywords: Myeloproliferative neoplasms, EZH2, CAL2, Immunohistochemistry
Classical BCR/ABL-1-negative myeloproliferative neoplasms (MPN) are hematopoietic stem cell disorders characterized by clonal proliferation of more than one mature myeloid cell lineage. The most common etiology is the constitutive activation of the JAK/STAT signalling pathway, caused by three main driver mutations: JAK2V617F, CALR, and MPL. In this study, we analyzed the distribution of these driver mutations in our series of classical BCR/AB1-negative MPN patients and their correlation with clinical symptoms, bone marrow, and laboratory findings. We also explored the efficacy of using the CAL2 antibody to identify CALR mutations and studied the potential of using EZH2 antibody expression levels as a prognostic indicator. Our study of 78 BCR/ABL1-negative MPN patients found JAK2V617 mutation in 57.7%, CALR mutation in 11.5%, and MPL mutation in 1.3% of cases. Thrombosis was the most common initial symptom, observed in 25% of patients, predominantly in those with JAK2V617F mutation (p= 0.02). CAL2 was positive in nearly all megakaryocytes of CALR mutant cases (7/9). EZH2 H-scores in egakaryocytes were lower in patients with a higher reticulin fibrosis score (p= 0.013), and thrombotic events were more frequently observed in these patients (p= 0.081). Our findings suggest that CAL2 and EZH2 immunohistochemical staining have potential as diagnostic and prognostic surrogate markers for MPN. Nevertheless, presently, the most crucial components in the diagnosis and prognosis of MPN are comprehensive molecular profiling and its alignment with other diagnostic tools.
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