Mutational landscape of myelodysplastic/myeloproliferative neoplasm–unclassifiable

Bose, Prithviraj; Nazha, Aziz; Komrokji, Rami; Patel, Keyur P.; Pierce, Sherry; Al-Ali, Najla; Sochacki, Andrew; Shaver, Aaron C.; Ma, Wencai; Su, Xiaoping; Daver, Naval; DiNardo, Courtney D.; Garcia‐Manero, Guillermo; Loghavi, Sanam; Bueso‐Ramos, Carlos E.; Kantarjian, Hagop M.; Sekeres, Mikkael A.; Savona, Michael R.; Maciejewski, Jaroslaw P.; Verstovšek, Srđan

doi:10.1182/blood-2018-05-848473

Cited by 41 publications

(45 citation statements)

References 25 publications

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“…De-Morgan et al studied the genomic data of 2773 MDS patients and showed that men have higher incidence of U2AF1 and ZSRS2 mutations whereas women with MDS have higher incidence of DNMT3A and TP53 mutations [ 8 ]. Bose et al, performed an analysis of the genomic landscape of 102 patients with unclassifiable MDS/MPN syndrome and further confirmed that women have a higher incidence of DNMT3A mutations while mutations in the ASXL1 gene were more common among men [ 31 ]. We recently studied the mutational landscape of 100 patients with MDS/MPN and found that men have a higher number of somatic mutations and higher frequency of mutations in the EZH2 gene independent of the specific disease sub-type (Karantanos et al, under review).…”

Section: Sex-related Differences In the Genomic Profile Of Patientmentioning

confidence: 99%

Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology

Karantanos

Jain

Moliterno

et al. 2021

IJMS

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Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. Different groups have highlighted that men have overall worse survival and higher incidence of transformation to acute leukemia compared to women across neoplasms such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap neoplasms, and CML. More recent studies evaluating the genomic profile of patients with these neoplasms demonstrated a male predominance for mutations in high-risk genes including ASXL1, U2AF1, SRSF2 and ZRSR2. The understanding of the underlying biology is limited but a number of hypotheses have been developed and are currently being investigated. This review summarizes the current knowledge about sex-related differences in the clinical outcomes and genomic profile of patients with chronic myeloid neoplasms and discusses the hypothesized biologic mechanisms as an attempt to explain these observations.

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Section: Sex-related Differences In the Genomic Profile Of Patientmentioning

confidence: 99%

Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology

Karantanos

Jain

Moliterno

et al. 2021

IJMS

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“…The International Prognostic Scoring System–Revised (IPSS-R) developed for MDS combined with cytogenetics is often used in clinical practice and studies, but its prognostic usefulness has been uncertain. 12 – 14 In contrast, Mangaonkar et al 11 found that both IPSS-R and Global MD Anderson (MDA) model successfully risk stratified 135 MDS/MPN-U patients at 3 years follow-up. Palomo et al 5 found that the presence of cytogenetic abnormalities was associated with an inferior overall survival (OS) in MDS/MPN neoplasms, except for aCML.…”

Section: Discussionmentioning

confidence: 99%

“… 7 , 17 In Table 3 , we have summarized the current knowledge regarding their prevalence and potential prognostic value in different myeloid malignancies. 5 , 7 , 12 , 16 , 19 – 23 However, due to the rarity of these disease entities and the low prevalence of some of the mutations, their prognostic values are uncertain. Future studies will enhance our knowledge in this regard.…”

Section: Discussionmentioning

confidence: 99%

Favorable outcome of a patient with an unclassifiable myelodysplastic syndrome/myeloproliferative neoplasm treated with allogeneic hematopoietic stem cell transplantation

Hemsing

Gjertsen

Spetalen

et al. 2021

SAGE Open Medical Case Reports

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The entity myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome is characterized by the coexistence of both myeloproliferative and myelodysplastic features in the bone marrow. Risk assessment and treatment recommendations have not been standardized, and clinicians rely on updated patient studies and reviews to make decisions for treatment approaches. Histopathological features have traditionally been important, although in the last decade, several studies have reported mutational profiles of this rare disease. Here, we present a case, wherein the patient presented with leukocytosis and the diagnostic work-up revealed features of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome. Mutational profiling revealed mutations in four genes associated with myeloid malignancies, namely, EZH2, CUX1, TET2, and BCOR. After initial therapy with hydroxyurea and interferon-α, the patient underwent allogeneic hematopoietic stem cell transplantation, with reduced intensity conditioning and a matched sibling donor. He had no signs of relapsed disease 2 years after the transplant. Based on the patient outcome, we summarize the diagnostic and therapeutic approaches for patients diagnosed with myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome, and review the current literature, emphasizing the role of genetic mutations and allogeneic hematopoietic stem cell transplantation. Larger and more detailed clinical studies are strongly needed to optimize and standardize diagnostic and therapeutic approaches for this disease.

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“…Whole genome and whole exome sequencing of hematologic malignancies (78)(79)(80)(81)(82)(83)(84)(85) has revealed the spectrum of fusions and mutations (also referred to as the mutanome) of these diseases, including events that range from rare to highly recurrent. Many of these genetic abnormalities may give rise to neoantigens.…”

Section: Shared Vs Personal Neoantigensmentioning

confidence: 99%

Neoantigens in Hematologic Malignancies

Biernacki

Bleakley

2020

Front. Immunol.

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T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid "on-target, off-tumor" toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing technology and innovations in antigen discovery approaches have facilitated the identification of neoantigens. In comparison to many solid tumors, hematologic malignancies have few mutations and thus fewer potential neoantigens. Despite this, neoantigens have been identified in a wide variety of hematologic malignancies. These include mutated nucleophosmin1 and PML-RARA in acute myeloid leukemia, ETV6-RUNX1 fusions and other mutated proteins in acute lymphoblastic leukemia, BCR-ABL1 fusions in chronic myeloid leukemia, driver mutations in myeloproliferative neoplasms, immunoglobulins in lymphomas, and proteins derived from patient-specific mutations in chronic lymphoid leukemias. We will review advances in the field of neoantigen discovery, describe the spectrum of identified neoantigens in hematologic malignancies, and discuss the potential of these neoantigens for clinical translation.

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Mutational landscape of myelodysplastic/myeloproliferative neoplasm–unclassifiable

Abstract: F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.

Cited by 41 publications

References 25 publications

Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology

Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology

Favorable outcome of a patient with an unclassifiable myelodysplastic syndrome/myeloproliferative neoplasm treated with allogeneic hematopoietic stem cell transplantation

Neoantigens in Hematologic Malignancies

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