Key Points: Within MDS/MPN, the WHO 2008 criteria for aCML identify a subgroup of patients with aggressive clinical features distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.

TP53 mutation is more prevalent in therapy-related myeloid neoplasms (t-MN) than their de novo counterparts; however, the pattern of mutations involving TP53 gene in t-MN versus de novo diseases is largely unknown. We collected 108 consecutive patients with therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML). Clinical, hematological, and cytogenetic data were collected by searching the electronic medical record. TP53 sequencing was performed in all patients using a clinically validated next-generation sequencing-based gene panel assay. A previously published patient cohort consisting of 428 patients with de novo MDS/AML was included for comparison. We assessed 108 patients with t-MN, in which 40 patients (37%) had TP53 mutations. The mutation frequency was similar between t-MDS and t-AML; but significantly higher than de novo MDS/AML (62/428 patients, 14.5%) (p < 0.0001). TP53 mutations in t-MN were mainly clustered in DNA-binding domains, with an allelic frequency of 37.0% (range, 7.1 to 98.8). Most mutations involved single nucleotide changes, of which, transitions (65.9%) were more common than transversions (34.1%). Missense mutations were the most frequent, followed by frameshift and nonsense mutations. This TP53 mutation pattern was strikingly similar to that observed in de novo MDS/AML. TP53 mutations in t-MN were associated with a complex karyotype (p < 0.0001), a higher number of chromosomal abnormalities (p < 0.0001), and an inferior overall survival in affected patients (6.1 vs 14.1 months) by univariate (p < 0.0001) and multivariate analyses (p = 0.0020). Our findings support the recent notion that heterozygous TP53 mutation may be a function of normal aging and that mutated cells are subject to selection upon exposure to cytotoxic therapy. t-MN carrying TP53 mutation have an aggressive clinical course independent of other confounding factors.

Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Following the current World Health Organization classification algorithm, these cases were classified as: 13 acute myeloid leukemia with myelodysplasia-related changes, 3 therapy-related acute myeloid leukemia, and 1 chronic myelogenous leukemia blast crisis, and one unclassifiable due to insufficient clinical information. All 16 cases with cytogenetic data harbored an extremely complex karyotype and the median overall survival of the 18 patients was 3 months (range, 1–7 months). This survival was significantly shorter than that of patients with acute erythroid leukemia, erythroid/myeloid subtype, or acute myeloid leukemia with myelodysplasia-related changes with erythroid predominance (P<0.001). PEL is characterized as a neoplastic erythroid hyperproliferation with maturation arrest. E-cadherin emerged as the most sensitive and specific marker for immature erythroblasts, and was helpful in distinguishing PEL from other erythroid proliferations. Our study showed that the criteria for acute myeloid leukemia in the 2008 World Health Organization system facilitate reclassification of PEL cases into other acute myeloid leukemia categories, mainly of acute myeloid leukemia with myelodysplasia-related changes. These new assigned categories fail to capture the distinct features of PEL, where the phenotype of PEL correlates with a very complex karyotype and an extremely aggressive clinical course.

BACKGROUND.: Conventional karyotype has an established role in myelodysplastic syndrome (MDS) and is included in the International Prognostic Scoring System (IPSS) for patient risk stratification and treatment selection. Although some chromosomal abnormalities have been well characterized, the significance of several miscellaneous, infrequent, single chromosomal abnormalities remains to be defined. In addition, the emerging therapeutic agents may change the natural course of disease in patients with MDS and the cytogenetic impact on risk stratification.METHODS.: Clinicopathologic data were retrieved on 1029 patients who had a diagnosis of primary MDS and had available cytogenetic data (karyotype) on file.RESULTS.: Cytogenetic abnormalities were identified in 458 patients (45%) and occurred most frequently in patients who had refractory anemia with excess blasts (62%). Overall, the 3 cytogenetic risk groups defined by the IPSS—good, intermediate, and poor—effectively stratified the patients' overall survival (OS) (64 months, 31 months, and 12 months, respectively; P < .001). With the exception of gain of chromosome 8, single cytogenetic abnormalities within the intermediate group were extremely infrequent in the series but demonstrated variable OS ranging from 10 months for patients who had isochromosome (17q) to 69 months for patients who had deletion of 12p [del(12p)], suggesting different prognostic significance. In the poor cytogenetic risk group, patients with isolated del(7q) and derivative (1;7)(q10;p10) had a significantly better median OS than patients who had either loss of chromosome 7 or a complex karyotype (P < .05).CONCLUSIONS.: The current data generated from a large cohort of patients with primary MDS indicated that some specific cytogenetic abnormalities carry different risk than their IPSS cytogenetic risk‐group assignment, especially in the new treatment era. Because of the extreme low frequency, additional combined studies are needed to better categorize some rare single cytogenetic abnormalities within the intermediate cytogenetic risk group. Cancer 2008. © 2008 American Cancer Society.

Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key end point in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the European LeukemiaNet (ELN) 2022 genetic risk classification. Developed by members of the ELN AML MRD Working Party, the guidelines incorporate expert consensus determined through a 2-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity next-generation sequencing–based MRD assessment is now recommended for FLT3 internal tandem duplication–mutated AML after intensive chemotherapy and before allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.