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Haematological malignancies in relatives of patients affected with myeloproliferative neoplasms.

ABSTRACT: In a cohort of 3131 patients with myeloproliferative neoplasms (MPNs), we identified 200 patients (6.4%) who reported a second case of haematological malignancies (HM) in first- or second-degree relatives. The occurrence of a second HM in the family was not influenced by MPN subtype, sex or driver mutation, while it was associated with age at MPN diagnosis: 8.5% of patients diagnosed with MPN younger than 45 years had a second relative affected with HM compared to 5.5% of those diagnosed at the age of 45 years or older (p = 0.003), thus suggesting a genetic predisposition to HM with early onset.

SUBMITTER: Vanni D

PROVIDER: S-EPMC9176120 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Haematological malignancies in relatives of patients affected with myeloproliferative neoplasms.

Vanni Daniele D Borsani Oscar O Nannya Yasuhito Y Sant'Antonio Emanuela E Trotti Chiara C Casetti Ilaria Carola IC Pietra Daniela D Gallì Anna A Zibellini Silvia S Ferretti Virginia Valeria VV Malcovati Luca L Ogawa Seishi S Arcaini Luca L Rumi Elisa E

EJHaem 20220324 2

In a cohort of 3131 patients with myeloproliferative neoplasms (MPNs), we identified 200 patients (6.4%) who reported a second case of haematological malignancies (HM) in first- or second-degree relatives. The occurrence of a second HM in the family was not influenced by MPN subtype, sex or driver mutation, while it was associated with age at MPN diagnosis: 8.5% of patients diagnosed with MPN younger than 45 years had a second relative affected with HM compared to 5.5% of those diagnosed at the ...[more]

PMID: 35846061

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Project description:Histiocytic disorders are a spectrum of rare diseases characterised by the accumulation of macrophage-, dendritic cell-, or monocyte-differentiated cells in various tissues and organs. The discovery of recurrent genetic alterations in many of these histiocytoses has led to their recognition as clonal neoplastic diseases. Moreover, the identification of the same somatic mutation in histiocytic lesions and peripheral blood and/or bone marrow cells from histiocytosis patients has provided evidence for systemic histiocytic neoplasms to originate from haematopoietic stem/progenitor cells (HSPCs). Here, we investigated associations between histiocytic disorders and additional haematological malignancies bearing the same genetic alteration(s) using the nationwide Dutch Pathology Registry. By searching on pathologist-assigned diagnostic terms for the various histiocytic disorders, we identified 4602 patients with a putative histopathological diagnosis of a histiocytic disorder between 1971 and 2019. Histiocytosis-affected tissue samples of 187 patients had been analysed for genetic alterations as part of routine molecular diagnostics, including from nine patients with an additional haematological malignancy. Among these patients, we discovered three cases with different histiocytic neoplasms and additional haematological malignancies bearing identical oncogenic mutations, including one patient with concomitant KRAS p.A59E mutated histiocytic sarcoma and chronic myelomonocytic leukaemia (CMML), one patient with synchronous NRAS p.G12V mutated indeterminate cell histiocytosis and CMML, and one patient with subsequent NRAS p.Q61R mutated Erdheim-Chester disease and acute myeloid leukaemia. These cases support the existence of a common haematopoietic cell-of-origin in at least a proportion of patients with a histiocytic neoplasm and additional haematological malignancy. In addition, they suggest that driver mutations in particular genes (e.g. N/KRAS) may specifically predispose to the development of an additional clonally related haematological malignancy or secondary histiocytic neoplasm. Finally, the putative existence of derailed multipotent HSPCs in these patients emphasises the importance of adequate (bone marrow) staging, molecular analysis and long-term follow-up of all histiocytosis patients.

Dataset Information

Haematological malignancies in relatives of patients affected with myeloproliferative neoplasms.

Publications

Haematological malignancies in relatives of patients affected with myeloproliferative neoplasms.

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