Clinicopathologic characteristics, prognostication and treatment outcomes for myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U): Mayo Clinic-Moffitt Cancer Center study of 135 consecutive patients

Mangaonkar, Abhishek A.; Swoboda, David M; Coltro, Giacomo; Lasho, Terra L.; Novotny, Paul J.; Pophali, Prateek; Carr, Ryan M.; Binder, Moritz; Finke, Christy; Gangat, Naseema; Al‐Kali, Aref; Begna, Kebede H.; Reichard, Kaaren K.; Ketterling, Rhett P.; Ali, Najla H Al; Vafaii, Pardis; Zhang, Ling; Padron, Eric; Talati, Chetasi; Patnaik, Mrinal M.

doi:10.1038/s41375-019-0574-x

Cited by 38 publications

(50 citation statements)

References 15 publications

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“…Among all MDS/MPN overlap syndromes, MDS/MPN-U is the subtype with the highest frequency of chromosome instability, with near 50% of altered karyotypes. Trisomy 8 (mostly found as a sole abnormality) is the most frequent alteration (15–25%), followed by chr7 alterations (12%) and CK (12%) [ 4 , 20 , 27 ]. Other less common abnormalities include del(12p), +9 and del(20q) [ 20 , 27 ].…”

Section: Cytogenetic Abnormalities In Mds/mpnmentioning

confidence: 99%

“…Trisomy 8 (mostly found as a sole abnormality) is the most frequent alteration (15–25%), followed by chr7 alterations (12%) and CK (12%) [ 4 , 20 , 27 ]. Other less common abnormalities include del(12p), +9 and del(20q) [ 20 , 27 ]. Overall, the presence of cytogenetic abnormalities is generally associated with an inferior OS in all adult MDS/MPN subtypes, except aCML [ 4 ].…”

Section: Cytogenetic Abnormalities In Mds/mpnmentioning

confidence: 99%

“…Molecular landscape of MDS/MPN-U is the most heterogeneous, which is expected given that this group includes a variety of poorly defined MDS/MPN that do not meet criteria for other well-defined subtypes, highlighting the complexity of categorization of overlap syndromes. Overall, the most frequent mutations include ASXL1 (40%), JAK2 (25%), TET2 (25%), SRSF2 (25%), EZH2 (20%), U2AF1 (16%) and RUNX1 (15%) [ 19 , 27 , 37 ] ( Figure 1 B). One study recently reported that different molecular profiles could be identified in MDS/MPN-U, which recapitulated molecular signatures that are significantly associated with other MDS/MPN entities [ 4 ].…”

Section: Molecular Landscape Of Mds/mpn and Clinical Implicationsmentioning

confidence: 99%

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Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

Palomo

Acha

Solé

2021

Cancers

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Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. Nevertheless, none of them is specific to MDS/MPN and current diagnostic criteria do not include molecular data. Even when such alterations can be helpful for differential diagnosis, they should not be used alone as proof of neoplasia because some of these mutations may also occur in healthy older people. Here, we intend to review the main genetic findings across all MDS/MPN overlap syndromes and discuss their relevance in the management of the patients.

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Section: Cytogenetic Abnormalities In Mds/mpnmentioning

confidence: 99%

Section: Cytogenetic Abnormalities In Mds/mpnmentioning

confidence: 99%

Section: Molecular Landscape Of Mds/mpn and Clinical Implicationsmentioning

confidence: 99%

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Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

Palomo

Acha

Solé

2021

Cancers

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“…11 Those models successfully stratified MDS/MPN-U patients for OS and leukaemia-free survival (LFS), and R-IPSS was more effective than others. 12 In this case, the patient was stratified as intermediate by R-IPSS. MDS/MPN-U is an incurable disease with poor outcome, and treatment continues to be challenging.…”

Section: Discussionmentioning

confidence: 99%

<p>Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of <em>KRAS</em></p>

Luo

et al. 2020

OTT

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Myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/ MPN-U) is a subtype of MDS/MPN that exhibits a combination of the features of both MDS and MPN. To date, no curative treatment is available for MDS/MPN-U; however, previous studies have suggested a potential survival advantage for ruxolitinib and hypomethylating agents. We reported a case of a JAK2-negative but KRAS-positive MDS/MPN-U patient treated with ruxolitinib plus decitabine. After treatment, the patient's clinical symptoms were moderated, and the size of the spleen and the peripheral blood cell counts were reduced. These effects might be due to the regimen's ability to reduce STAT5 activation and upregulate microRNA-181c to downregulate the variant allele frequency (VAF) of KRAS.

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“…15% of the patients[27,80,86,111,[113][114][115]. TP53 mutations have been reported in 8-9% of cases, higher than what is reported in other MDS/MPNs, while a variety of other genes recurrently mutated across myeloid malignancies are seen at low frequencies[27,114,115]. The common driver mutations of MPN (i.e., JAK2, CALR, MPL) tend to exclude the diagnosis since they may be seen in MPN cases or in the disease progression.…”

mentioning

confidence: 98%

Myelodysplastic syndromes and overlap syndromes

Chang

2021

Blood Res

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological neoplasms characterized by ineffective hematopoiesis, morphologic dysplasia, and cytopenia. MDS overlap syndromes include various disorders, such as myelodysplastic/myeloproliferative neoplasms and hypoplastic MDS with aplastic anemia characteristics. MDS overlap syndromes share the characteristics of other diseases, which make differential diagnoses challenging. Advances in genomic studies have led to the discovery of frequent mutations in MDS and overlap syndromes; however, most of the mutations are not specific for the diagnosis of these diseases. The molecular characteristics of the overlap syndromes usually do not show a just “in-between” form but rather heterogeneous features. Established diagnostic criteria for these diseases based on clinical, morphologic, and laboratory features are still useful when combined with genomic data. It is expected that further studies for MDS and overlap syndromes will place emphasis on the roles of mutations as therapeutic targets and prognostic indicators.

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Clinicopathologic characteristics, prognostication and treatment outcomes for myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U): Mayo Clinic-Moffitt Cancer Center study of 135 consecutive patients

Cited by 38 publications

References 15 publications

Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

<p>Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of <em>KRAS</em></p>

Myelodysplastic syndromes and overlap syndromes

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