Genomic stratification of myelodysplastic/myeloproliferative neoplasms, unclassifiable: Sorting through the unsorted

Mangaonkar, Abhishek A.; Swoboda, David M; Lasho, Terra L.; Finke, Christy; Ketterling, Rhett P.; Reichard, Kaaren K.; Padron, Eric; Talati, Chetasi; Patnaik, Mrinal M.

doi:10.1038/s41375-021-01258-6

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…Patients with MDS/MPN‐NOS can be further stratified based on their somatic mutation profile and phenotype into five categories: (a) CMML‐like (biallelic TET2 , TET2/SRSF2 and RUNX1/SRSF2 mutations), (b) aCML‐like ( ASXL1/SETBP1 , ASXL1/SRSF2 , ASXL1/EZH2 and RUNX1/EZH2 mutations), (c) MDS/MPN‐RS‐T‐like ( SF3B1 , DNMT3A/SF3B1 , SF3B1/JAK2 and DNMT3A/JAK2 mutations), (d) TP53 mutant (monoallelic and multi‐hit TP53 states), and (e) others ( CBL and STAG2 ) (Figure 3). 9,27 In a large study that included 106 patients, this system effectively stratified patients into CMML‐like 17%, aCML‐like 33%, MDS/MPN‐RS‐T like 12%, TP53 mutant (13%), and others (26%), respectively. 9 This stratification resulted in survival rates similar to individual overlap entities, with MDS/MPN‐RS‐T‐like patients having the best outcomes (median not reached), followed by CMML‐like patients (median not reached), others (median 80.3 months), and aCML‐like patients (median 18.8 months), with TP53 mutant cases having the worst outcomes (median 5.2 months).…”

Section: Disease Overviewmentioning

confidence: 99%

“…(Figure 3). 9,27 In a large study that included 106 patients, this system effectively stratified patients into CMML-like 17%, aCML-like 33%, MDS/MPN-RS-T like 12%, TP53 mutant (13%), and others (26%), respectively. 9 This stratification resulted in survival rates similar to individual overlap entities, with MDS/MPN-RS-T-like patients having the best outcomes (median not reached), followed by CMML-like patients (median not reached), others (median 80.3 months), and aCML-like patients (median 18.8 months), with TP53 mutant cases having the worst outcomes (median 5.2 months).…”

Section: Cytogenetic Abnormalities and Gene Mutationsmentioning

confidence: 99%

“…(now considered a provisional category by the ICC schema). [27][28][29] In a large Mayo Clinic-Moffit Cancer Center study, somatic mutations identified included ASXL1 (58%), SRSF2 (37%), SETBP1 (19%), JAK2 (18%), TET2 (15%), NRAS (13%), EZH2 (12%), RUNX1 (10%), SF3B1 (10%), GATA2 (9%), TP53 (7%), STAG2 (7%), ZRSR2 (6%), CBL (6%), MPL, FLT3, and IDH1 (4% each), and U2AF1 (3%), respectively. (Figure 3).…”

Section: Cytogenetic Abnormalities and Gene Mutationsmentioning

confidence: 99%

“…9 In the large Mayo Clinic-Moffitt Cancer Center study (n = 140), using the same molecular stratification schema, the median survival for individual categories was MDS/MPN-RS-T-like 170 months (range: 1, 170), CMML-like 44 months (range: 12, median NR), others 28 months (range: 24, 35), aCML-like 19 months (range: 1, 23), and TP53 mt 10.5 months (range: 4, 24), respectively. 27 While molecular risk stratification is useful for prognostication, MDS-risk models, such as the International Prognostic Scoring System (IPSS), Revised-IPSS (IPSS-R), and the Global MD Anderson Prognostic Scoring System, have all been used comparably to risk stratify patients, with the IPSS-R being particularly effective in risk stratifying patients belonging to the "Others" category. 27,28,33,34 Of note, the ties and discussed elsewhere.…”

Section: Cytogenetic Abnormalities and Gene Mutationsmentioning

confidence: 99%

“…27 While molecular risk stratification is useful for prognostication, MDS-risk models, such as the International Prognostic Scoring System (IPSS), Revised-IPSS (IPSS-R), and the Global MD Anderson Prognostic Scoring System, have all been used comparably to risk stratify patients, with the IPSS-R being particularly effective in risk stratifying patients belonging to the "Others" category. 27,28,33,34 Of note, the ties and discussed elsewhere. 30,31 Given the highly aggressive nature of TP53 mutant cases, allogeneic HCT should be encouraged in appropriate recipients.…”

Section: Cytogenetic Abnormalities and Gene Mutationsmentioning

confidence: 99%

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Atypical chronic myeloid leukemia and myelodysplastic/myeloproliferative neoplasm, not otherwise specified: 2023 update on diagnosis, risk stratification, and management

Patnaik

Tefferi

2023

American J Hematol

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Disease Overview Atypical chronic myeloid leukemia (aCML) and myelodysplastic/myeloproliferative (MDS/MPN) neoplasms, not otherwise specified (NOS), are MDS/MPN overlap neoplasms characterized by leukocytosis, in the absence of monocytosis and eosinophilia, with <20% blasts in the blood and bone marrow. Diagnosis aCML, previously known as aCML, BCR::ABL1 negative, was renamed as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the 5th edition of the WHO classification. This entity is characterized by dysplastic neutrophilia with immature myeloid cells comprising ≥10% of the white blood cell count, with prominent dysgranulopoiesis. MDS/MPN‐NOS consists of MDS/MPN overlap neoplasms not meeting criteria for defined categories such as chronic myelomonocytic leukemia (CMML), MDS/MPN‐ring sideroblasts‐thrombocytosis (MDS/MPN‐RS‐T), and aCML. Mutations and Karyotype Cytogenetic abnormalities are seen in 40–50% of patients in both categories. In aCML, somatic mutations commonly encountered include ASXL1, SETBP1, ETNK1, and EZH2 whereas MDS/MPN‐NOS can be further stratified by mutational profiles into CMML‐like, MDS/MPN‐RS‐T‐like, aCML‐like, TP35‐mutated, and “others”, respectively. Risk Stratification The Mayo Clinic aCML model stratifies patients based on age >67 years, hemoglobin <10 g/dl, and the presence of TET2 mutations into low‐risk (0–1 points) and high‐risk (>2 points) groups, with median survivals of 18 and 7 months, respectively. MDS/MPN‐NOS patients have traditionally been risk stratified using MDS risk models such as IPSS and IPSS‐R. Treatment Leukocytosis and anemia are managed like lower risk MPN and MDS. DNMT inhibitors have been used in both entities with suboptimal response rates. Allogeneic stem cell transplant remains the only curative strategy but is associated with high morbidity and mortality.

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Section: Disease Overviewmentioning

confidence: 99%