TY - JOUR

T1 - Case Report

T2 - First longitudinal study of a patient with CALR positive clonal hematopoiesis of indeterminate potential developing into pre-fibrotic myelofibrosis

AU - Kjær, Lasse

AU - Skov, Vibe

AU - Larsen, Morten Kranker

AU - Boklund, Tobias Idor

AU - Andersen, Morten

AU - Kefala, Maria

AU - Knudsen, Trine A.

AU - Schjellerup Eickhardt-Dalbøge, Christina

AU - Stiehl, Thomas

AU - Gudmand-Høyer, Johanne

AU - Snyder, Jordan

AU - Holmström, Morten

AU - Andersen, Mads H.

AU - Ottesen, Johnny T.

AU - Ellervik, Christina

AU - Hasselbalch, Hans C.

N1 - Publisher Copyright: Copyright © 2023 Kjær, Skov, Larsen, Boklund, Andersen, Kefala, Knudsen, Schjellerup Eickhardt-Dalbøge, Stiehl, Gudmand-Høyer, Snyder, Holmström, Andersen, Ottesen, Ellervik and Hasselbalch.

PY - 2023

Y1 - 2023

N2 - Initial diagnosis of overt myeloproliferative neoplasms (MPNs) represents the juncture during clonal evolution when symptoms or complications prompt an afflicted individual to seek medical attention. In 30-40% of the MPN subgroups essential thrombocythemia (ET) and myelofibrosis (MF), somatic mutations in the calreticulin gene (CALR) are drivers of the disease resulting in constitutive activation of the thrombopoietin receptor (MPL). In the current study, we describe a healthy CALR mutated individual during a 12 year follow-up from initial identification of CALR clonal hematopoiesis of indeterminate potential (CHIP) to the diagnosis of pre-MF. The pre-diagnostic exponential development dynamics of the malignant clone demonstrated close correlation with the platelet counts, neutrophil-to-lymphocyte (NLR) ratio, and inversely correlated to hemoglobin and erythrocyte counts. Backward extrapolation of the growth rate indicated the potential for discovery of the malignant clone many years prior to presentation of overt disease, opening a window of opportunity for early treatment intervention. We did not find any additional mutations associated with MPNs and the current case report provides novel information regarding the development of a driver mutation and the association with blood cell counts prior to clinical manifestation of symptoms suggesting that pre-diagnostic dynamics may supplement future diagnostic criteria for early diagnosis and intervention in MPN patients.

AB - Initial diagnosis of overt myeloproliferative neoplasms (MPNs) represents the juncture during clonal evolution when symptoms or complications prompt an afflicted individual to seek medical attention. In 30-40% of the MPN subgroups essential thrombocythemia (ET) and myelofibrosis (MF), somatic mutations in the calreticulin gene (CALR) are drivers of the disease resulting in constitutive activation of the thrombopoietin receptor (MPL). In the current study, we describe a healthy CALR mutated individual during a 12 year follow-up from initial identification of CALR clonal hematopoiesis of indeterminate potential (CHIP) to the diagnosis of pre-MF. The pre-diagnostic exponential development dynamics of the malignant clone demonstrated close correlation with the platelet counts, neutrophil-to-lymphocyte (NLR) ratio, and inversely correlated to hemoglobin and erythrocyte counts. Backward extrapolation of the growth rate indicated the potential for discovery of the malignant clone many years prior to presentation of overt disease, opening a window of opportunity for early treatment intervention. We did not find any additional mutations associated with MPNs and the current case report provides novel information regarding the development of a driver mutation and the association with blood cell counts prior to clinical manifestation of symptoms suggesting that pre-diagnostic dynamics may supplement future diagnostic criteria for early diagnosis and intervention in MPN patients.

KW - CALR

KW - case report

KW - clonal hematopoiesis

KW - MPN

KW - myelofibrosis

UR - http://www.scopus.com/inward/record.url?scp=85159894770&partnerID=8YFLogxK

U2 - 10.3389/fonc.2023.1176173

DO - 10.3389/fonc.2023.1176173

M3 - Journal article

C2 - 37223675

AN - SCOPUS:85159894770

VL - 13

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

M1 - 1176173

ER -