Diagnosis Of Acute Myeloid Leukemia Research Articles

Erythroblastosis Transformation-Specific Regulated Gene 1 (ERG) Immunohistochemistry in the Diagnosis of Acute Myeloid Leukemia

Erythroblastosis Transformation-Specific Regulated Gene 1 (ERG) Immunohistochemistry in the Diagnosis of Acute Myeloid Leukemia

FLT3-MUTATED ACUTE MYELOID LEUKEMIA OUTCOMES IN A NORTHEAST BRAZILIAN UNIVERSITY HOSPITAL

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 25-45% of new diagnoses of Acute myeloid leukemia. The addition of FLT3 inhibitors to conventional protocols improves overall survival in this condition. Objectives: To assess the incidence of FLT3 gene mutation among patients diagnosed with AML at Walter Cantídio University Hospital; Describe access to FLT3 inhibitors and bone marrow transplantation (BMT), and the overall survival of this group. Methodology: Retrospective evaluation of medical records of patients treated for AML between 2020 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 47 patients were diagnosed with AML during this period, of whom 17% had FLT3+ mutation. 3/8 patients accessed FLT3 inhibitors. The median survival with FLT3+ mutation was 9.1 months vs. 12.9 months in FLT3- (p = 0.196). The overall survival of AML patients was 30.9% at 2 years. 11/47 patients underwent allogeneic BMT. Conclusion: The addition of targeted therapies and BMT may contribute to reduce mortality in AML. Elderly patients and those not undergoing HSCT have worse outcomes.

Management of hyperleukocytosis in pediatric acute myeloid leukemia using immediate chemotherapy without leukapheresis: results from the NOPHO-DBH AML 2012 Protocol.

Hyperleukocytosis (HL) in pediatric acute myeloid leukemia (AML) is associated with severe complications and inferior outcome. We report results on HL patients included in the NOPHO-DBH AML 2012 study. We recommended immediate start of full dose chemotherapy (etoposide [ETO] monotherapy for 5 days as part of the first course), avoiding leukapheresis (LA) and prephase chemotherapy (PCT). Of 714 included patients, 122 (17.1%) had HL, and 111 were treated according to the recommendations with ETO upfront without preceding LA or PCT. The first dose was applied the same day as the AML diagnosis or the day after in 94%. ETO was administered via peripheral veins in 37% of patients without major complications. After initiation of ETO the remaining WBC on days 2-5 was 69%, 36%, 17% and 8% of the pre-treatment level. On day 3, 81% had a WBC.

Immunophenotypic clustering in paediatric acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations. Cox regression analysis unveiled key antigens influencing the prognosis of AML patients. In terms of underlying genotypes, we observed that the antigenic profiles and outcomes of one specific group, primarily composed of CBFA2T3::GLIS2 and FUS::ERG, were analogous to the reported RAM phenotype. Overall, our data highlight the significance of immunophenotype to tailor treatment for paediatric AML.

Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial

Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial

Факторы риска развития рецидивов перианальных инфекционных осложнений у пациентов с опухолевыми заболеваниями системы крови: результаты одноцентрового проспективного исследования

Aim. To study risk factors for relapses of perianal infection (PI) in patients with hematological tumors.
 Materials & Methods. This single-center prospective clinical trial (2016–2020) enrolled all oncohematological patients at the National Research Center for Hematology who developed PI at various stages of chemotherapy. To assess the impact of some factors on relapsing perianal infectious complications, the distribution of clinical characteristics in groups of patients with single or multiple PI episodes was analyzed.
 Results. The trial addressed 158 PI episodes in 132 patients; there were 64 men and 68 women, the median age was 40 years (range 18–77 years). PI relapses were identified in 22 (16.67 %) patients, with a higher incidence in acute myeloid leukemia (AML) patients (63.64 %). Recurrent PI episodes were usually registered on program therapy of acute leukemias (73.08 %), more often at consolidation stage (38.46 %) than at other stages of treatment (17.42 %) (hazard ratio [HR] 2.96; 95% confidence interval [95% CI] 1.19–7.35; p < 0.031). With the follow-up of 360 days from the first episode, the probability of PI relapses was 16.2 %, and it was higher in AML patients (24.3 %). In non-remission AML patients having the first PI episode, the probability of PI relapses considerably increased and accounted for 52.6 %. In case of cryptogenic pararectal abscesses, it was 20 %, if solely abscess drainage was performed at the first stage. However, no relapses were registered after the surgical treatment of pararectal fistulas. The risk factors for recurrent PI, as was shown by univariate analysis, were AML diagnosis (HR 2.94; 95% CI 1.14–7.62; p < 0.032) and the lack of remission of hematological tumor by the time of the first PI episode (HR 2.98; 95% CI 1.13–7.90; p < 0.034). By multivariate analysis, the significant risk factor was non-remission AML diagnosis by the time of the first PI episode (HR 6.94; 95% CI 2.93–16.66; p < 0.0001).
 Conclusion. The significant risk factor for PI relapses is non-remission AML diagnosis by the time of the first infectious episode. This category of patients shows the maximal probability of relapsing perianal infectious complications, which is 52.6 %. To prevent PI relapses in patients with cryptogenic pararectal abscesses, abscess drainage should be combined with scheduled surgery of anal fistulas.

A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy.

DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls. Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS. The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukaemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with cachectic hallmarks. Biological samples and clinical data were collected from 30 antibiotic-free AML patients at diagnosis and matched volunteers (1:1) in a multicenter cross-sectional prospective study. The composition and functional potential of the faecal microbiota were analyzed using shotgun metagenomics. Faecal, blood, and urine metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycaemic disorders. The composition of the faecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and faecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g. Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycaemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

Comparison of the WHO classification (5th edition) 2022 and the International Consensus Classification (ICC) 2022 for diagnosis of acute myeloid leukemia)

In 2022, two classifications were published to define the diagnosis of patients with acute myeloid leukemia (AML). The World Health Organisation (WHO) 5th edition and the International Consensus Classification (ICC) provide an updated summary of current knowledge of the diseases and construct a framework for physicians. Two differing classifications result in discrepancies, which change the definition of AML subtypes and present a challenge in clinical settings. This work summarizes the updated classification systems and discusses their significance in clinical settings while considering the latest findings. Relevant changes affect the i) required blast percentage, ii) AML harbouring CEBPA mutations, iii) AML with KMT2A and MECOM rearrangements, iv) AML with myelodysplasia-related characteristics and in association with this entity AML with mutated RUNX1, and lastly v) AML with TP53 mutation. In summary, a unified classification system would be desirable to achieve harmonized diagnosis and treatment of AML).

Acute Myeloid Leukemia in a Three-Year-Old Girl Mimicking Chronic Myeloid Leukemia in Blast Crisis, Challenge in Diagnosis and Treatment in Limited-Resourced Health Care Facility: A Case Report

Introduction: : Acute myeloid leukemia (AML) is the second most common hematologic cancer in childhood. Clinically, AML has similar symptoms to other types of leukemias, and diagnosis remains a challenge due to limited access to pediatric hemato-oncology diagnostic examination. This study aims to report AML in a 3-year-old girl who was first suspected of Chronic Myeloid Leukemia (CML) in blast crisis, using a combination of clinical-hematology parameters and conventional morphology examination in a limited-resourced healthcare facility. Case Presentation: A 3-year-old girl was referred from a rural Eastern Indonesia hospital with symptoms of prolonged fever, leucocytosis, severe anemia, and severe thrombocytopenia. In the previous hospital, the patient had a history of hyperleukocytosis and peripheral blood smear suspected of CML in blast crisis. A peripheral blood smear was repeated in our hospital and showed findings of Auer rod cells suggesting AML. Two bags of packed red cells and 2 thrombocyte concentrations were administered before referral for further diagnostic evaluation with bone marrow aspiration. Bone marrow aspiration revealed multiple nucleoli suggested for AML with FAB classification as M4 subtypes, and she received chemotherapy in a tertiary hospitalConclusions: With limited resources, suspicion based on persistent clinical symptoms, routine hematology tests, and peripheral blood smear examination are important to distinguish AML from CML in blast crisis. Understanding clinical hematology parameters and peripheral blood smears is the first step in AML diagnosis pathway and decision for further diagnostic referral. Supportive therapy and early recognition of oncologic emergency must be done before referral to a tertiary referral hospital.

Transcriptome free energy can serve as a dynamic patient-specific biomarker in acute myeloid leukemia

Acute myeloid leukemia (AML) is prevalent in both adult and pediatric patients. Despite advances in patient categorization, the heterogeneity of AML remains a challenge. Recent studies have explored the use of gene expression data to enhance AML diagnosis and prognosis, however, alternative approaches rooted in physics and chemistry may provide another level of insight into AML transformation. Utilizing publicly available databases, we analyze 884 human and mouse blood and bone marrow samples. We employ a personalized medicine strategy, combining state-transition theory and surprisal analysis, to assess the RNA transcriptome of individual patients. The transcriptome is transformed into physical parameters that represent each sample’s steady state and the free energy change (FEC) from that steady state, which is the state with the lowest free energy.We found the transcriptome steady state was invariant across normal and AML samples. FEC, representing active molecular processes, varied significantly between samples and was used to create patient-specific barcodes to characterize the biology of the disease. We discovered that AML samples that were in a transition state had the highest FEC. This disease state may be characterized as the most unstable and hence the most therapeutically targetable since a change in free energy is a thermodynamic requirement for disease progression. We also found that distinct sets of ongoing processes may be at the root of otherwise similar clinical phenotypes, implying that our integrated analysis of transcriptome profiles may facilitate a personalized medicine approach to cure AML and restore a steady state in each patient.

Acute myeloid leukemia: An unusual manifestation of the trachea.

Hematologic malignancy involving the trachea is rare. It is even less common for tracheal involvement to be the initial manifestation of this disease. We present a case report highlighting an unusual diagnosis of acute myeloid leukemia (AML) that first presented with prominent tracheal manifestations. There have been only three other published case reports of extramedullary AML with involvement of the trachea. We discuss direct laryngoscopy and bronchoscopy findings, including pinkish-white irregular lesions, which were similar to findings described in the available literature for tracheal AML. Laboratory findings from our case are reported, including peripheral smear demonstrating 57% blasts and bone marrow biopsy confirming the diagnosis of AML, and the relevance of these findings is discussed. In patients with unusual airway lesions, laboratory testing and a comprehensive airway evaluation including biopsy are necessary to narrow the differential diagnosis. 5.

Abstract 6471: Trends in chemotherapy utilization in acute myeloid leukemia (AML) in last 15 years

Abstract Introduction: Chemotherapy (Chemo) can relieve symptoms and improve quality of life and survival in AML, including in many older and frail adults. However, in a prior study from the US, almost a quarter of patients (pts) with new diagnoses of AML between years (yrs) 2003 and 2011 did not receive chemo (Bhatt et al., Blood Advances, 2018). Our study examined trends in chemo utilization in the last 15 yrs to test the hypothesis that chemo use has increased in more recent yrs. We also examined any disparities in chemo use. Methods: We utilized the National Cancer Database to identify 78,864 pts diagnosed with AML between 2004 and 2019 and divided them into 2 cohorts based on date of diagnosis, 2004-2010 and 2011-2019. We used logistic regression to estimate effect of demographic and disease characteristics on odds of receiving chemo and evaluate differences in these effects between the constructed patient cohorts. Results: Seventy-seven percent of total pts received chemo. Compared to 73% in 2004, 81% of pts received chemo in 2019. The receipt of chemo declined with increasing age with higher use of chemo in all groups in 2011-2019 compared to 2004-2010: >80 (yrs)= 40 vs 33%, 71-80 yrs= 72 vs 63%, 60-70 yrs= 87 vs 84%, 41-59 yrs= 93 vs 92%, and 18-40 yrs = 95 vs 94%.The receipt of chemo was lowest in white pts overall; in black pts, receipt of chemo increased in 2011-2019 compared to 2004-2010: black= 83 vs 76%, white= 78 vs 75%, and others 83 vs 83%. The receipt of chemo was lowest in therapy-related (t)-AML in 2011-2019 and 2004-2010: t-AML 64 vs 60%, acute promyelocytic leukemia= 88 vs 87%, core binding factor AML 93 vs 88% and other 77 vs 74%. In multivariable analysis, the odds of receiving chemo increased in 2011-2019 compared to 2004-2010 in all pts, particularly in older adults. Compared to white, black pts had similar odds of receiving chemo in 2004-2010, but odds were higher in 2011-2019 (Odds ratio, 1.2, 95% confidence interval, 1.1-1.3. Pts with t-AML were less likely to receive chemo compared to all other subtypes in 2004-2010 and 2011-2019. Female sex, lower income, public insurance, higher comorbidity score, and shorter distance to treatment facility were associated with a lower likelihood of receiving chemo; however, chemo utilization did not differ over the two time periods based on these variables. Conclusion: To our knowledge, this is the largest scale analysis of chemo utilization in AML in real-world practice. Chemo receipt increased significantly over the yrs, particularly among older adults, black pts, core binding factor, and t-AML. These recent trends are encouraging and represent novel findings. Despite these results, healthcare disparity based on sex, socioeconomic, and healthcare system factors continues to persist. In addition to developing safer and more effective chemo regimens, other innovative strategies to tackle these disparities are crucial to improve outcomes. Citation Format: Prajwal Dhakal, Bradley Loeffler, Aditya Ravindra, Avantika Pyakuryal, Vijaya Raj Bhatt. Trends in chemotherapy utilization in acute myeloid leukemia (AML) in last 15 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6471.

Abstract 3954: Increased mosaic chromosomal alterations among survivors of childhood acute myeloid leukemia

Abstract Background: We previously characterized point mutations of clonal hematopoiesis (CH) including single nucleotide variants or small insertion/deletions residing in a set of cancer-related genes (e.g., DNMT3A and TET2), and found that CH point mutations occurred at a much higher prevalence in childhood cancer survivors (CCS) than in age-sex-race matched community controls. However, mosaic chromosomal alterations (mCAs), another form of CH with megabase-scale structural alterations (copy gain, copy loss and copy-neutral loss of heterozygosity), have not been examined. Methods: Detection of mCAs was performed on whole-genome sequencing (WGS, 30X) data from 5-year CCS with the Mosaic Chromosomal Alterations (MoChA) caller which utilizes phased genotypes, coverage, and B allele frequency (BAF) at heterozygous sites (HETS). We implemented the pipeline established by the TOPMed consortium to detect low mutant cell fractions (CF ≥1%). Variant filtration criteria: minor allele frequency <1%, the read depth of either allele <5, and only one variant retained in each 1Kb window. Called mCA filtration criteria: <100 HETS; lod score <5; relative coverage >2.9 or BAF deviation >0.16 and relative coverage >2.5. Autosomal mCAs (CF ≥1%, HETS >100 and length >1Mb) retained. Multivariable Cox models evaluated the association between mCAs and specific late-effects including all-cause mortality, obesity, myocardial infarction (MI) or cardiomyopathy (CMP); multivariable logistic models evaluated the association between mCAs and childhood cancer diagnoses. All models were adjusted for age, sex and therapeutic exposures. Results: In our evaluation of 4,330 CCS (median age at blood draw: 26.8 years) and 433 controls (33.6 years) with WGS data from the St. Jude Lifetime Cohort, the prevalence of mCAs was slightly higher among CCS than community controls (4.83% vs. 4.16%). Among CCS, mCAs were associated with therapeutic exposures (alkylating agents: odds ratio [OR]=1.48, 95% CI=1.09-2.00; antimetabolites: 1.53, 1.02-2.31; corticosteroids: 0.60, 0.40-0.91). In contrast to recent mCA studies in the general population, we observed no co-occurrence with CH point mutations, and no associations with late-effects including all-cause mortality, obesity, MI or CMP. Interestingly, mCAs were significantly associated with the primary diagnosis of acute myeloid leukemia (AML, OR=2.86, 95% CI=1.63-5.01). Furthermore, this finding was replicated in 2898 5-year survivors from the Childhood Cancer Survivor Study (OR=3.77, 95% CI=1.94-7.33). Conclusion: mCAs were not associated with age-related morbidities and mortality among CCS. However, we identified a striking association between mCAs and previous diagnoses of AML independent of treatment exposures. If validated among AML patients at the time of diagnosis, mCAs, which reflect the underlying genome instability, may serve as a diagnostic biomarker for AML. Citation Format: Xijun Zhang, Na Qin, Qian Dong, Cheng Chen, John Easton, Heather Mulder, Xiang Chen, Kyla Shelton, Cindy Im, Yutaka Yasui, Greg Armstrong, Kirsten K. Ness, Melissa M. Hudson, Paul Auer, Jinghui Zhang, Zhaoming Wang. Increased mosaic chromosomal alterations among survivors of childhood acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3954.

CLEC11A methylation is correlated to AML subtypes and cytogenetic risk factors but not patient demographics.

Acute myeloid leukemia (AML) is an aggressive and lethal cancer of the blood, which leads to the death of over 11,000 patients in the United States each year. Research on identifying, characterizing, and treating AML is crucial in the fight against this deadly disease. Recent studies have examined the role of CLEC11A in cancer, including AML. However, there have been conflicting reports related to tumor progression and survival. Because survival is based on a variety of factors, including classification of the tumor, genetic risk factors, and demographics, it is imperative that we determine what role CLEC11A may have in cancer survival. Therefore, utilizing data from the Genomic Data Commons, we analyzed CLEC11A methylation in 108 AML patients compared to FAB classification, cytogenetic risk factors, age, race, and gender. Our results show statistically significant correlations between methylation of CLEC11A and FAB classification as well as poor genetic risk factors. However, no difference was observed in CLEC11A methylation when compared to demographic data. Our results, matched with a known biological function of CLEC11A in early hematopoiesis, indicate that CLEC11A may be an important marker for AML diagnosis and prognosis and provide relevant data in the ongoing search for novel therapeutics to improve AML survival.

AC024896.1/miR-363-3p Axis Regulates the Malignant Progression of Acute Myeloid Leukemia by Cuproptosis-Related Gene MYO1B.

Acute myeloid leukemia (AML) is a hematological malignancy with poor patient prognosis. Cuprotosis is a newly discovered cell death that regulates the proliferation and progression of tumor cells. Long non-coding RNAs (lncRNAs) are key molecules and potential biomarkers for the diagnosis and treatment of various diseases. However, the effect of cuprotosis-associated lncRNAs on AML remains unclear. The aim of this study was to investigate the relationship between the expression of cuprotosis-related gene and the prognosis of AML. Consensus cluster analysis was performed on AML patients according to the cuprotosis-related gene expression matrix, and survival analysis and differential gene analysis were performed. Then lncRNA and miRNA related to AML tumor progression were screened according to univariate COX regression analysis. After that, Kaplan-Meier analysis, correlation analysis, and AUC curve were used to determine the ceRNA network that might regulate AML. The regulatory relationship of ceRNA was verified in AML cell lines by RT-qPCR and Western blotting. The AC024896.1/miR-363-3p axis drives MYO1B to promote the malignant progression of AML. First, a change in the expression of AC024896.1 and miR-363-3p can affect the proliferation of AML by regulating MYO1B. Mechanistically, AC024896.1 regulates the expression of MYO1B as the ceRNA of miR-363-3p. Moreover, the regulation of AC024896.1 in the malignant progression of AML depends partly on miR-363-3p. In summary, our study reveals AC024896.1/miR-363-3p/MYO1B Axis in AML, which can be regarded as a new potential target for the diagnosis and treatment of AML.

Long noncoding RNA LINC00675 drives malignancy in acute myeloid leukemia via the miR-6809 -CDK6 axis

Hematological malignancies such as acute myeloid leukemia (AML) have a low cure rate and a high recurrence rate. Long noncoding RNAs (LNCs) are essential regulators of tumorigenesis and progression. The role of lncRNA LINC00675 in AML has rarely been reported. This study revealed elevated LINC00675 expression in AML that promotes proliferation and inhibits apoptosis. Mechanistically, LINC00675 combines with miR-6809 to promote the expression of CDK6 in vitro and in vivo. Immune-checkpoint genes were expressed more highly in LINC00675-high patients. A high level of LINC00675 expression may make patients more susceptible to palbociclib treatments. In conclusion, our study demonstrated that LINC00675 is an oncogenic lncRNA that enhances the malignancy of AML by upregulating CDK6 expression through miR-6809 sponging, providing a new perspective and feasible target for the diagnosis and treatment of AML.

Work absenteeism, disability, and lost wages among patients with acute myeloid leukemia and their caregivers: a cohort study using US administrative claims and productivity data

ABSTRACT Objective We describe the impact of acute myeloid leukemia (AML) diagnosis on workplace absenteeism and disability days among patients and their caregivers. Methods This retrospective study included adults with newly diagnosed AML (2009–2019) and adult caregivers of patients with newly diagnosed AML, identified from the US Merative™ MarketScan® Commercial Database. The Merative MarketScan Health and Productivity Management Database provided linked patient-level records of workplace absence and short-term (STD) and long-term disability (LTD) data. Endpoints included workplace absence, STD and LTD for patients and caregivers during 12 months pre-AML (baseline) and ≤3 years’ follow-up, and corresponding cost of work loss. Results Patient workplace absence decreased in the months post-AML diagnosis, but the number of STD and LTD leave days claimed increased significantly by sixfold and fourfold, respectively. The proportion of patients making STD leave claims increased within 4–5 months of diagnosis, while the proportion making LTD leave claims increased significantly starting from month 5. Caregiver workplace absence peaked in the first 2 months post-diagnosis and remained elevated versus baseline throughout the study. Conclusion AML diagnosis leads to workplace absenteeism and increased economic burden for patients with AML and their caregivers.

Construction of an Immune-Related Prognostic Signature and lncRNA‒miRNA-mRNA ceRNA Network in Acute Myeloid Leukaemia.

The progression of acute myeloid leukaemia (AML) is influenced by the immune microenvironment in the bone marrow and dysregulated intracellular competing endogenous RNA (ceRNA) networks. Our study utilized data from UCSC Xena, Cancer Genome Atlas Program, Gene Expression Omnibus, Immunology Database and Analysis Portal. Using Cox regression analysis, we identified an immune-related prognostic signature. Genomic analysis of prognostic mRNA was conducted through Gene Set Cancer Analysis (GSCA), and a prognostic ceRNA network was constructed using the Encyclopedia of RNA Interactomes. Correlations between signature mRNAs and immune cell infiltration, checkpoints, and drug sensitivity were assessed using R software, GEPIA, and CellMiner, respectively. Adhering to the ceRNA hypothesis, we established a potential lncRNA/miRNA/mRNA regulatory axis. Our findings pinpointed nine immune-related prognostic mRNAs (KIR2DL1, CSRP1, APOBEC3G, CKLF, PLXNC1, PNOC, ANGPT1, IL1R2, and IL3RA). GSCA analysis revealed the impact of copy number variations and methylation on AML. The ceRNA network comprised 14 differentially expressed prognostic lncRNAs (DE-lncRNAs), six prognostic DE-miRNAs, and three prognostic immune-related IR-DEmRNAs. Correlation analyses linked these mRNA's expression to 22 immune cell types, six immune checkpoints, and potential sensitivity to 27 antitumor drugs. Finally, we identified a potential LINC00963/hsa-miR-431-5p/CSRP1 axis. This study offers innovative insights for AML diagnosis and treatment through a novel immune-related signature and ceRNA axis. Identified novel biomarkers, including two mRNAs (CKLF, PNOC), one miRNA (hsa-miR-323a-3p), and ten lncRNAs (SNHG25, LINC01857, AL390728.6, AC127024.5, Z83843.1, AP002884.1, AC007038.1, AC112512, AC020659.1, AC005921.3) present promising candidates as potential targets for precision medicine, contributing to the ongoing advancements in the field.

Evidence for identification of acute myeloid leukemia using peripheral blood's infrared spectrum and logistic regression

Invasive damage, poor prognosis and survival are problems for the traditional diagnostic and therapeutic methods of acute myeloid leukemia (AML), especially for the middle-aged and elderly. High sensitivity, less pain and fast speed are demands of AML diagnosis or long-term regular monitoring. Infrared (IR) spectroscopy has the potential to compensate for existing deficiencies and is explored in our work. Spectral differences between AML patients and controls are observed on the IR spectra, which indicate the changes in lipids and proteins in patients. The peak shift at 1390 cm−1 occurs on both peripheral blood (PB) and bone marrow (BM) spectra of AML patients making it possible to use PB rather than BM as the diagnostic source, which can relieve the suffering of diagnosis and monitoring. The logistic regression-based classification model can perfectly identify AML patients and controls with an accuracy of 100 % and the area under curve is equal to 1.00. Besides, some markers for identifying AML patients and controls are found. Statistical analysis shows that the peak area ratio A1451/A1390 has a significant difference, and the decision tree-based classification model finds that on the first derivative spectrum, the position of the largest difference is at 1391 cm−1. Furthermore, the proposed criterion based on markers we found can distinguish AML patients and controls with high accuracy of 95 %. Results show that PB’s IR spectrum combined with classification models can monitor the molecular-level biochemical changes and accurately identify AML patients and controls, which is helpful for the effective and efficient diagnosis and prognosis of AML.