Secondary Acute Myeloid Leukemia (sAML): Similarly Dismal Outcomes of AML After an Antecedent Hematologic Disorder and Therapy Related AML

Lalayanni, Chrysavgi; Gavriilaki, Eleni; Athanasiadou, Anastasia; Iskas, Michail; Παπαθανασίου, Μαρία; Marvaki, Anastasia; Mpesikli, Sotiria; Παπαϊωάννου, Γεώργιος; Mallouri, Despina; Batsis, Ioannis; Papalexandri, Apostolia; Sakellari, Ioanna; Anagnostopoulos, Achilles

doi:10.1016/j.clml.2021.09.019

Cited by 10 publications

(13 citation statements)

References 33 publications

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“…There were no significant difference between sAML-AHD and t-AML in terms of gender, CR achievement, refractory rates, relapse rates and early death. [11] These findings aligned with data from a Danish national population-based cohort study, which showed that "sAML" patients were older, had lower CR rates, and poorer survival compared to patients with de novo AML. Additionally, patients with sAML-AHD were more likely to have intermediate cytogenetics than patients with t-AML.…”

Section: Discussionsupporting

confidence: 77%

Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review

Gao,

Han,

Jiang

et al. 2023

Medicine

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Rationale: Because there are few evidence-based guidelines and an extremely low incidence rate, managing and treating patients who have transitioned from acute promyelocytic leukemia (APL), which was diagnosed during pregnancy, to acute myeloid leukemia (AML), can be difficult. Patient concerns: In this case, a 34-year-old pregnant patient was diagnosed with APL in medium-risk group in June 2017. After the all-trans retinoic acid and arsenic trioxide-based full-course treatment, the patients achieved complete remission (CR) and were well-tolerated. After 5 years, the patient complained of fatigue for 3 months. Diagnosis: Bone marrow examination revealed hypercellularity with approximately 50% immunophenotypic abnormal myeloblasts with MLL-AF9 fusion gene. Based on the AML diagnosis criteria of the World Health Organization, the patient was eventually diagnosed with a rare transformation from APL to AML. Interventions: The patient was treated with two cycles of induction chemotherapy and an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Outcomes: Until now, the patient is in continuous remission with no signs of APL and AML. Lessions: Despite the rarity of APL to AML transformation, it is crucial to track the disease’s progress and administer treatment on time. It remains uncertain whether the risk stratification and clinical outcomes of secondary AML with MLL-AF9 are equivalent to those of de novo AML with MLL-AF9. The management and treatment of these patients should be personalized and require further observation.

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Section: Discussionsupporting

confidence: 77%

Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review

Gao,

Han,

Jiang

et al. 2023

Medicine

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“…The designation of ontogeny as either MR-Hx/MR-CG or t-AML has clinical implications. Many studies have shown that "secondary" AML, mostly MR-Hx/MR-CG and t-AML, is associated with an inferior outcome with or without allo-HSCT 16,33,34,[36][37][38][39][40] . Our study has confirmed these findings by showing MR-Hx, MR-CG and t-AML all confer worse outcomes than de novo AML even after adjusting for age, treatment, transplant, and ELN risks.…”

Section: Discussionmentioning

confidence: 99%

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

McCarter

Nemirovsky

Famulare

et al. 2022

Preprint

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Accurate classification and risk stratification is critical for clinical decision making in AML patients. In the newly proposed World Health Organization (WHO) and International Consensus classifications (ICC) of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as one of the diagnostic criteria of AML, myelodysplasia-related (AML-MR), largely based on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined by clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations to the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed AML patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), we show that ontogeny assignment based on database registry lacks accuracy. MR gene mutations are frequently seen in de novo AML. Among MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in a univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also stratified the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny and questions the current classification and risk stratification of AML with MR gene mutations.

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“…Proteomic and phosphoproteomic profiles were available for a consecutive subset of 15 younger AML patients (below 60 years of age), and we compared two contrasting patient groups with an antiproliferative effect corresponding to a relative response (i.e., the proliferation in the presence of bafilomycin A 10 nM being) <0.30 versus >0.60, respectively. These comparisons therefore included eight strong responders (Tables S1 and S2; patients 5,15,55,59,64,69,71) and seven weak responders (Table S1, patients 2, 23,31,34,36,41,51,73).…”

Section: Aml Cell Proliferation: Possible Protein Biomarkers For Susc...mentioning

confidence: 99%

“…Secondary AML includes patients with antecedent myeloid malignancies or previous exposure to cytotoxic treatment, and clinical studies have shown that these patients have reduced AML-free survival after intensive therapy [50][51][52][53][54][55][56][57][58][59] due to chemoresistance and increased relapse risk [2,60]. The strong responders showed a significantly increased frequency of patients with secondary/relapsed AML (17 out of 37 patients, see Table S2) compared with the intermediate/weak responders (6 out of 33 patients; Fisher's exact test, p = 0.0211).…”

mentioning

confidence: 99%

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

Bartaula-Brevik,

Leitch,

Hernandez-Valladares

et al. 2023

JCM

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Vacuolar ATPase (V-ATPase) is regarded as a possible target in cancer treatment. It is expressed in primary acute myeloid leukemia cells (AML), but the expression varies between patients and is highest for patients with a favorable prognosis after intensive chemotherapy. We therefore investigated the functional effects of two V-ATPase inhibitors (bafilomycin A1, concanamycin A) for primary AML cells derived from 80 consecutive patients. The V-ATPase inhibitors showed dose-dependent antiproliferative and proapoptotic effects that varied considerably between patients. A proteomic comparison of primary AML cells showing weak versus strong antiproliferative effects of V-ATPase inhibition showed a differential expression of proteins involved in intracellular transport/cytoskeleton functions, and an equivalent phosphoproteomic comparison showed a differential expression of proteins that regulate RNA processing/function together with increased activity of casein kinase 2. Patients with secondary AML, i.e., a heterogeneous subset with generally adverse prognosis and previous cytotoxic therapy, myeloproliferative neoplasia or myelodysplastic syndrome, were characterized by a strong antiproliferative effect of V-ATPase inhibition and also by a specific mRNA expression profile of V-ATPase interactome proteins. Furthermore, the V-ATPase inhibition altered the constitutive extracellular release of several soluble mediators (e.g., chemokines, interleukins, proteases, protease inhibitors), and increased mediator levels in the presence of AML-supporting bone marrow mesenchymal stem cells was then observed, especially for patients with secondary AML. Finally, animal studies suggested that the V-ATPase inhibitor bafilomycin had limited toxicity, even when combined with cytarabine. To conclude, V-ATPase inhibition has antileukemic effects in AML, but this effect varies between patients.

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Secondary Acute Myeloid Leukemia (sAML): Similarly Dismal Outcomes of AML After an Antecedent Hematologic Disorder and Therapy Related AML

Cited by 10 publications

References 33 publications

Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review

Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

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