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Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms.

ABSTRACT: BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations are acquired in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells in peripheral blood and fibrosis in bone marrow. Mutations in JAK2, MPL, and CALR are frequently found in BCR::ABL1-negative MPNs, and detecting typical mutations in these three genes has become essential for the diagnosis of BCR::ABL1-negative MPNs. Furthermore, comprehensive gene mutation and expression analyses performed using massively parallel sequencing have identified gene mutations associated with the prognosis of BCR::ABL1-negative MPNs such as ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1. Furthermore, single-cell analyses have partially elucidated the effect of the order of mutation acquisition on the phenotype of BCR::ABL1-negative MPNs and the mechanism of the pathogenesis of BCR::ABL1-negative MPNs. Recently, specific CREB3L1 overexpression has been identified in megakaryocytes and platelets in BCR::ABL1-negative MPNs, which may be promising for the development of diagnostic applications. In this review, we describe the genetic mutations found in BCR::ABL1-negative MPNs, including the results of analyses conducted by our group.

SUBMITTER: Morishita S

PROVIDER: S-EPMC10455804 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms.

Morishita Soji S Komatsu Norio N

International journal of molecular sciences 20230821 16

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations are acquired in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells in peripheral blood and fibrosis in bone marrow. Mutations in JAK2, MPL, and CALR are frequently found in BCR::ABL1-negative MPNs, and detecting typical mutations in these three genes has become essential for the diagnosis of BCR::ABL1< ...[more]

PMID: 37629188

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Project description:IntroductionThe identification of specific molecular signatures and the development of new targeted drugs have changed the paradigm of onco-nephrology, now allowing a multiscale approach of kidney involvement related to hematologic malignancies relying on combined hematologic and molecular assessments. In this study, we aimed to refine the spectrum of kidney disorders associated with chronic myelomonocytic leukemia (CMML) or BCR-ABL-negative myeloproliferative neoplasms (MPNs), 2 very rare conditions scarcely described.MethodsCase series. Patients with myeloid neoplasms who were referred to Toulouse University Hospital Nephrology Unit and were diagnosed with acute kidney injury (AKI), chronic kidney disease (CKD), or urine abnormalities were retrospectively included.ResultsEighteen patients (males n=13, CMML n=8, essential thrombocytosis [ET] n=7, polycythemia vera [PV] n=1, and myelofibrosis n=2) developed kidney disease 7.7±2 years after the diagnosis of the malignancy. Twelve patients had AKI at presentation. Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy (n=14) showed various patterns, including pauci-immune glomerulosclerosis (n=5), extramedullary hematopoiesis (n=6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation (n=8). Immunostaining of CD61 confirmed the infiltration of megakaryocytes within glomeruli or interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy n=2, AA amyloidosis n=1). Massive kidney infiltration by CMML was identified in 1 patient. After a mean follow-up of 24±6 months, malignancy was considered as stable in 11 patients (61%), but 22% of patients had progressed to end-stage renal failure. The remaining had persistently reduced kidney function. No correlation between the malignancy and the renal presentation and outcomes could be identified.ConclusionsKidney complications of CMML/MPN are heterogenous, and kidney biopsy may help to identify new molecular targets to prevent the development of kidney fibrosis.

Dataset Information

Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms.

Publications

Diagnosis- and Prognosis-Related Gene Alterations in <i>BCR::ABL1</i>-Negative Myeloproliferative Neoplasms.

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