Expression of <scp>CD</scp>4 is correlated with an unfavorable prognosis in wild‐type <scp>NPM</scp>1, <scp>FLT</scp>3‐<scp>ITD</scp>‐negative cytogenetically normal adult acute myeloid leukemia

Guo, Robert J.; Atenafu, Eshetu G.; Schimmer, Aaron D.; Minden, Mark D.; Chang, Hong

doi:10.1111/ijlh.12649

Cited by 5 publications

(3 citation statements)

References 38 publications

(58 reference statements)

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“…The prognostic role value of CD4 expression in AML is unclear. A recent study showed that CD4 expression was correlated with an unfavourable prognosis in NPM1 wt /FLT3-ITD neg and cytogenetically normal AML [32]. In contrast, CD4 positivity in our analysis was an independent prognostic marker for achieving a CR after induction therapy in univariable and multivariable analyses, but, surprisingly, did not translate into favourable survival rates.…”

Section: Discussioncontrasting

confidence: 83%

Prevalence and clinical impact of CD56 and T‐cell marker expression in acute myeloid leukaemia: A single‐centre retrospective analysis

Shaforostova,

Call,

Evers

et al. 2023

eJHaem

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Flow cytometry‐based immunophenotyping is a mainstay of diagnostics in acute myeloid leukaemia (AML). Aberrant CD56 and T‐cell antigen expression is observed in a fraction subset of AML cases, but the clinical relevance remains incompletely understood. Here, we retrospectively investigated the association of CD56 and T‐cell marker expression with disease‐specific characteristics and outcome of 324 AML patients who received intensive induction therapy at our centre between 2011 and 2019. We found that CD2 expression was associated with abnormal non‐complex karyotype, NPM1 wild‐type status and TP53 mutation. CD2 also correlated with a lower complete remission (CR) rate (47.8% vs. 71.6%, p = 0.03). CyTdT and CD2 were associated with inferior 3‐year event‐free‐survival (EFS) (5.3% vs. 33.5%, p = 0.003 and 17.4% vs. 33.1%, p = 0.02, respectively). CyTdT expression was also correlated with inferior relapse‐free survival (27.3% vs. 48.8%, p = 0.04). In multivariable analyses CD2 positivity was an independent adverse factor for EFS (HR 1.72, p = 0.03). These results indicate a biological relevance of aberrant T‐cell marker expression in AML and provide a rationale to further characterise the molecular origin in T‐lineage‐associated AML.

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Section: Discussioncontrasting

confidence: 83%

Prevalence and clinical impact of CD56 and T‐cell marker expression in acute myeloid leukaemia: A single‐centre retrospective analysis

Shaforostova,

Call,

Evers

et al. 2023

eJHaem

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“…Altogether, it is evident that the genetic diversity of NPM1 -mutated AML should be examined in terms of its mutational landscape and clonal evolution for better patient-specific treatment needs. Likewise understanding the immunophenotypic markers (e.g., CD4, CD34, and CD56) of patients can better understand immune resistance and escape mechanisms in AML [ 164 , 165 ]. One possible non-conventional strategy is meditation, which has been linked to 68 genes modulating interferon signalling [ 166 ].…”

Section: Targeting Npm1 -Mutated Amlmentioning

confidence: 99%

Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (NPM1) Mutation

Chin

Wong

Gill

2023

IJMS

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Mutations in NPM1, also known as nucleophosmin-1, B23, NO38, or numatrin, are seen in approximately one-third of patients with acute myeloid leukaemia (AML). A plethora of treatment strategies have been studied to determine the best possible approach to curing NPM1-mutated AML. Here, we introduce the structure and function of NPM1 and describe the application of minimal residual disease (MRD) monitoring using molecular methods by means of quantitative polymerase chain reaction (qPCR), droplet digital PCR (ddPCR), next-generation sequencing (NGS), and cytometry by time of flight (CyTOF) to target NPM1-mutated AML. Current drugs, now regarded as the standard of care for AML, as well as potential drugs still under development, will also be explored. This review will focus on the role of targeting aberrant NPM1 pathways such as BCL-2 and SYK; as well as epigenetic regulators (RNA polymerase), DNA intercalators (topoisomerase II), menin inhibitors, and hypomethylating agents. Aside from medication, the effects of stress on AML presentation have been reported, and some possible mechanisms outlined. Moreover, targeted strategies will be briefly discussed, not only for the prevention of abnormal trafficking and localisation of cytoplasmic NPM1 but also for the elimination of mutant NPM1 proteins. Lastly, the advancement of immunotherapy such as targeting CD33, CD123, and PD-1 will be mentioned.

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“…During follow-up, the detection of measurable residual disease by MFC is now part of most large clinical trials [9,10]. Several antigens, including CD34, CD4, CD56, CD7, and CD25, have been reported to be predictors of the general prognosis of AML patients [11][12][13][14][15]. However, reports have been rather conflicting, and incorporation of MFC data in clinical decision-making is indeed sparse [16].…”

Section: Introductionmentioning

confidence: 99%

Antigen Expression Varies Significantly between Molecular Subgroups of Acute Myeloid Leukemia Patients: Clinical Applicability Is Hampered by Establishment of Relevant Cutoffs

et al. 2020

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Introduction: In this single-center study of 268 acute myeloid leukemia (AML) patients, we have tested if a subset of 4 routinely employed immunophenotypic stem cell-associated markers correlated with the presence of recurrently mutated genes and if the markers were predictive for mutational status. Methods: Immunophenotypic data from 268 diagnostic AML samples obtained in 2009–2018 were analyzed retrospectively for the antigens CD34, CD117, CD123, and CLEC12A. Correlation between immunophenotypes and mutations was analyzed by Fischer’s exact test. Clinical applicability of the markers for predicting mutational status was evaluated by receiver operating characteristics analyses, where an area under the curve (AUC) of at least 0.85 was accepted as clinically relevant. Results: For a number of genes, the antigen expression differed significantly between mutated and wild-type gene expression. Despite low AUCs, CD123 and CLEC12A correlated with FLT3+NPM1− and FLT3+NPM1+. Three subsets met the AUC requirements (CD34+, CD34+CD117+, and CD34−CD117+) for predicting FLT3−NPM1+ or FLT3+NPM1+. Conclusion: The value of immunophenotypes as surrogate markers for mutational status in AML seems limited when employing CD123 and CLEC12A in combination with CD34 and CD117. Defining relevant cutoffs for given markers is challenging and hampered by variation between laboratories and patient groups.

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Expression of CD4 is correlated with an unfavorable prognosis in wild‐type NPM1, FLT3‐ITD‐negative cytogenetically normal adult acute myeloid leukemia

Abstract: Our results indicate that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML.

Cited by 5 publications

References 38 publications

Prevalence and clinical impact of CD56 and T‐cell marker expression in acute myeloid leukaemia: A single‐centre retrospective analysis

Prevalence and clinical impact of CD56 and T‐cell marker expression in acute myeloid leukaemia: A single‐centre retrospective analysis

Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (NPM1) Mutation

Antigen Expression Varies Significantly between Molecular Subgroups of Acute Myeloid Leukemia Patients: Clinical Applicability Is Hampered by Establishment of Relevant Cutoffs

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