ABSTRACT
The evolution of acute myeloid leukemia (AML) classifications has progressively shifted the diagnostic focus toward genetic criteria. Nevertheless, morphology remains a key element in clinical practice, often serving as the initial trigger for additional molecular investigations. The diagnosis of acute erythroleukemia (AEML), initially defined by the FAB group, is no longer recognized as a distinct entity in the latest WHO and ICC classifications. Some studies have indicated that AEML shares similarities with myelodysplastic neoplasms, including a high frequency of TP53 mutations and adverse karyotypes. Here, we conducted a retrospective analysis in adults with AEML defined using historical morphologic criteria (≥ 50% erythroid precursors and ≥ 20% blasts among non‐erythroid cells). In contrast to older patients, young adults (18–60 years) exhibit unique genetic profiles including a high prevalence of normal karyotypes (65%), NPM1 (35%) and UBTF (23%) mutations. AEML morphology in NPM1‐mutated cases did not impact clinical outcomes but was associated with specific molecular features, including an enrichment of WT1 and cohesin gene mutations. In this age group, our findings support that morphologically defined AEML often corresponds to AML according to current genetic criteria, consistent with recent classification systems that prioritize molecular features over morphology.
Keywords: AML, classification, erythroleukemia, NPM1, UBTF
1. Introduction
As knowledge in genetics has increased, the boundary between myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) has gradually blurred, and morphology has become a secondary parameter in disease classification. However, morphology remains an essential guiding factor in clinical practice and often serves as the initial basis for requesting further molecular investigations.
The disease entity formerly known as acute erythroleukemia (erythroid/myeloid; AEML) is a rare morphologic subtype of AML, originally named after Giovanni Di Guglielmo's description in 1917 of a patient with an abnormal proliferation of erythroid cells, myeloblasts, and megakaryocytes [1]. AEML was classified as AML of M6 type (M6‐AML) according to the French‐American‐British (FAB) classification in 1976 [2]. In its classification, the FAB group proposed to distinguish M6‐AML from MDS by assessing the percentage of bone marrow (BM) blasts among non‐erythroid cells, i.e., by excluding erythroblasts from the count. The diagnosis of AEML/M6‐AML required 30% or more of the non‐erythroid cells to be blast cells, which was lowered to 20% in the 2001 classification of the World Health Organization (WHO) [3].
In the 2016 WHO classification, AEML was removed from the AML category, as subsequent studies suggested it shared many features with MDS such as multilineage dysplasia, adverse cytogenetics, and TP53 mutations [4, 5]. The diagnosis of AML has since relied on a blast percentage calculated on total nucleated BM cells and on the identification of specific molecular abnormalities [6, 7, 8].
Here, we deliberately used the 2001 WHO criteria (i.e., presence of ≥ 50% erythroid precursors and ≥ 20% blasts among non‐erythroid cells) [3] to retrospectively select a well‐defined cohort of adult patients historically diagnosed with AEML in order to revisit this morphologically defined group using modern genetic tools. Cases that met the criteria for pure erythroid leukemia were excluded from the study. All patients were included in the French Hauts‐de‐France (HDF) AML observatory and the Acute Leukemia French Association (ALFA)‐0702 trial. Our findings showed that, in young adults (18–60 years old), cases historically classified as AEML exhibit molecular profiles that differ from those observed in older patients.
2. Materials and Methods
2.1. Patients
Patients were included from two separate cohorts: [1] The French Hauts‐de‐France (HDF)‐AML observatory is a population‐based database reporting adult (> 18 years old) AML cases, including secondary AML, diagnosed in 9 Hospital Centers from the French region Haut‐de‐France (Lille University Hospital, Amiens‐Picardie University Hospital, St Vincent‐de‐Paul Hospital Centre, Valenciennes Hospital Centre, Roubaix Hospital Centre, Lens Hospital Centre, Dunkerque Hospital Centre, Boulogne‐sur‐mer Hospital Centre and Arras Hospital Centre). Patients were registered between 2008 and 2022. Clinical data were collected by clinical research associates in each center, and biological samples were centralized and stored in the French National Cancer Institute labeled Tumor Bank of the Lille University Hospital (certification NF 96900‐2014/65453‐1). The database is registered by the Commission nationale de l'informatique et des libertés (identifier 2214454v0). [2] The ALFA‐0702 trial (clinicaltrials.gov, #NCT00932412) was a phase 2 multicenter randomized study including 18 to 60‐year‐old patients with newly diagnosed de novo AML. In this trial, AML diagnosis could be made in patients meeting FAB criteria of M6‐AML. From March 2009 to September 2013, 713 patients were included in the trial, and 565 were classified with FAB criteria, among which 29 had M6‐AML/AEML. Results of the ALFA‐0702 trial were previously published [9, 10]. It should be noticed that FAB criteria were adapted in both cohorts to the 2001 WHO classification, considering a blast threshold of 20% instead of 30% [3]. This study was approved by an Institutional Review Board and conducted in accordance with the Declaration of Helsinki.
2.2. Cytomorphology
BM smears from BM aspiration of 21 AEML/M6‐AML patients were centrally reviewed by two referral morphologists in Amiens hospital. All BM samples underwent May Giemsa Grunwald staining. A total of 500 nucleated cells were counted on the BM smears. Dysmegakaryopoiesis, dyserythropoiesis, and dysgranulopoiesis were considered assessable if the minimum number of analyzed megakaryocytes, erythroid, and granulocytic cells was 30, 200, and 200, respectively, according to WHO guidelines [11]. Dysplastic features were quantified using 17 criteria as previously described [12].
2.3. Cytogenetics and Molecular Analyses
Chromosome banding analysis was performed according to standard methods. Mutational screening was performed by high‐throughput sequencing by two distinct panels. For patients from the HDF‐AML observatory, libraries were prepared using the Ampliseq System according to the manufacturer's instructions and run on Ion Proton (Thermofisher, Waltham, MA, USA). For patients from the ALFA‐0702 study, libraries were prepared using Haloplex Target Enrichment System (Agilent Technologies) according to the manufacturer's instructions and run on MiSeq (Illumina). Variant interpretation was performed considering minor allele frequencies in the public Genome Aggregation Database of polymorphisms (variants with minor allele frequency > 0.02 in overall population/global ancestry or subcontinental ancestry were excluded) and variant allele frequencies (VAFs). Frameshift and nonsense variants were always considered relevant mutations, and additional in silico predictions were performed whenever possible on missense and splicing variants. Analyzes were focused on the 36 genes shared by both approaches and included ASXL1, BCOR, BCORL1, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PHF6, PTPN11, RAD21, RIT1, RUNX1, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, STAG2, TET2, TP53, U2AF1, WT1, ZRSR2. Additionally, KMT2A partial tandem duplications (KMT2A‐PTD) and recurrent fusion transcripts (including NPM1::MLF1) were screened by ligation‐dependent RT‐PCR amplification assay (LD‐RT‐PCR) [13]. FLT3‐internal tandem duplications (ITD) and UBTF‐tandem duplications (TD) were screened by fragment analysis as previously described [10, 14].
2.4. Statistics
Variables are reported as numbers and percentages or median and interquartile range (IQR). Comparisons of categorical and continuous variables were made with Fisher exact and Mann–Whitney U tests, respectively. Overall survival (OS) was defined from inclusion until death or last follow‐up. Disease‐free survival (DFS) was defined from the date of complete remission (CR) or CR with incomplete platelet recovery to the date of relapse or death (whichever came first) or until last follow‐up. Survival was analyzed with the Kaplan–Meier method and compared by the log‐rank test/by a univariable Cox's model. Survival outcomes were not censored for allogeneic hematopoietic cell transplantation. All tests were two‐sided; statistical significance was defined as a p‐value < 0.05, and statistical analyzes were performed with R software 4.1.2 (cran.r‐project.org).
3. Results
3.1. Cohort Description
A total of 82 patients with a diagnosis of AEML were identified, including 53 from the HDF‐AML observatory and 29 from the ALFA‐0702 study (Figure S1). The cohort was then divided into younger adults (18–60 years old) and older adults (> 60 years old), comprising 45 and 37 individuals respectively.
Among older adults (> 60 years), 13 (35%) had a prior history of myeloid malignancies (MDS, n = 7 or myeloproliferative neoplasms, n = 6) and 3 others (8%) had previously received chemotherapy for a solid tumor (Table S1). Karyotype was available for 32/37 patients and was complex (≥ 3 unrelated chromosome abnormalities) for 23 (72%), normal for 7 (22%) and with other abnormality for 2 (6%). Molecular analyzes were available in 22/37 patients and demonstrated TP53 mutations in 10 (including 9 with complex cytogenetics) and NPM1 mutations in 5 (all with normal karyotype).
We then focused our study on 45 young adults aged 18–60 years old with AEML (Table 1). Only one patient had a history of malignancy and prior exposure to genotoxic therapy. All but one received intensive chemotherapy after AEML diagnosis. Among them, 31 were males (sex ratio 2.2:1). Median age at diagnosis was 42 years (IQR: 37–55 years). Median BM blast infiltration (available in 43/45 patients) was 20% of total BM nucleated cells (IQR: 11.5%–24.5%). Seven patients (16%) displayed less than 10% BM blasts. Centralized morphological analysis (n = 19 young adults) showed dysmegakaryopoiesis, dyserythropoiesis, and dysgranulopoiesis in 92% (11/12), 95% (18/19) and 78% (14/18) of cases for which the corresponding lineage could be assessed. Hypogranulated granulocytes, erythroblasts with nuclear abnormalities, and megakaryocytes with separated nuclei were the most prominent dysplastic features in each lineage (Table S2). Cytogenetics was available in all but one patient. Two patients were excluded from subsequent molecular analyzes because of missing genomic DNA.
TABLE 1.
Characteristics of young adults with AEML at diagnosis.
| Cohort | HDF‐AML obs. | ALFA‐0702 | All |
|---|---|---|---|
| Patients, n | 16 | 29 | 45 |
| Age (y), median (range) | 45 (39–57) | 41 (37–52) | 42 (37–55) |
| Sex (M/F) | 10/6 | 21/8 | 31/14 |
| Blood counts | |||
| WBC (×109/L), median (range) | 2.1 (1.2–3.3) | 2.4 (1.5–4.5) | 2.2 (1.4–4.5) |
| Neutrophils (×109/L), median (range) | 1 (0.6–1.4) | 1.2 (0.5–1.7) | 1 (0.6–1.6) |
| Hemoglobin (g/dL), median (range) | 8.1 (7.4–8.7) | n/a | 8.1 (7.4–8.7) |
| Platelets (×109/L), median (range) | 57 (29.3–91) | 48 (28–68) | 49 (28–77) |
| BM blasts (%), median (range) | 11.5 (8.8–20) | 20 (16–25) | 20 (11.5–24.5) |
| Ontogeny | |||
| de novo, n (%) | 15 (94) | 29 (100) | 44 (98) |
| post‐MN, n (%) | 0 | 0 | 0 |
| t‐AML, n (%) | 1 (6) | 0 | 1 (2) |
| Karyotype | |||
| Available, n (%) | 16 (100) | 28 (97) | 44 (98) |
| Normal, n (%) | 8 (50) | 21 (75) | 29 (66) |
| Complex, n (%) | 3 (19) | 2 (7) | 5 (11) |
| t (3;5), n (%) | 1 (6) | 2 (7) | 3 (7) |
| Other abnormal, n (%) | 4 (25) | 3 (11) | 7 (16) |
| Main molecular lesions | |||
| Available, n (%) | 16 (100) | 27 (93) | 43 (96) |
| NPM1, n (%) | 4 (25) | 11 (41) | 15 (35) |
| WT1, n (%) | 8 (50) | 5 (19) | 13 (30) |
| UBTF‐TD, n (%) | 4 (25) | 6 (22) | 10 (23) |
| NRAS, n (%) | 2 (13) | 7 (26) | 9 (21) |
| TET2, n (%) | 2 (13) | 5 (19) | 7 (16) |
| STAG2, n (%) | 3 (19) | 2 (7) | 5 (12) |
| TP53, n (%) | 3 (19) | 2 (7) | 5 (12) |
| BCOR, n (%) | 1 (6) | 3 (11) | 4 (9) |
| DNMT3A, n (%) | 1 (6) | 3 (11) | 4 (9) |
| SMC3, n (%) | 1 (6) | 3 (11) | 4 (9) |
| FLT3‐ITD, n (%) | 2 (13) | 1 (4) | 3 (7) |
| IDH1, n (%) | 0 (0) | 3 (11) | 3 (7) |
| KMT2A‐PTD, n (%) | 1 (6) | 2 (7) | 3 (7) |
| KRAS, n (%) | 1 (6) | 2 (7) | 3 (7) |
| NPM1::MLF1, n (%) | 1 (6) | 2 (7) | 3 (7) |
| PHF6, n (%) | 0 (0) | 3 (11) | 3 (7) |
| PTPN11, n (%) | 2 (13) | 1 (4) | 3 (7) |
| RAD21, n (%) | 0 (0) | 3 (11) | 3 (7) |
| U2AF1, n (%) | 0 (0) | 3 (11) | 3 (7) |
Abbreviations: n/a, not available; post‐MN, post‐myeloid malignancy; t‐AML, therapy‐related.
3.2. AEML Features in Young Adults
Among young adults with available karyotype (n = 44), 29 (66%) had normal cytogenetics and only 5 (11%) had a complex karyotype. Three patients (7%) harbored a balanced t(3;5) (q25;q34) translocation leading to an NPM1::MLF1 fusion confirmed by LD‐RT‐PCR. Seven others (16%) had a non‐complex abnormal karyotype including 4 (9%) with an isolated trisomy 8. The classification of the young adult cohort with AEML according to the current criteria set by the WHO and the International Consensus Classification (ICC) in 2022 is depicted in Figure 1A. Patient distribution based on ICC criteria [8] was AML 56%, MDS/AML 27%, and MDS 17%. According to WHO criteria [7], the distribution was AML 63% and MDS 37% (MDS‐IB2 17%). The molecular landscape of the 43 young adults with available DNA is shown in Figure 1B. Molecular analyzes revealed that 15 (35%) had an NPM1 mutation and 10 (23%) had a tandem duplication in UBTF (UBTF‐TD), both of which define distinct entities [14, 15]. The most common additional mutation was WT1 in 13 patients (30%). Five patients (12%) had TP53 mutations (all of them harboring complex cytogenetics) and 3 others (7%) had a KMT2A‐PTD.
FIGURE 1.
AEML in young adults (18–60 years). (A) Classification of the AEML patients according to ICC 2022 and WHO criteria (n = 41 patients for whom data were available) The categories of AML in the ICC and WHO classifications are colored grey. MDS or MDS/AML categories (for ICC) are in white. (B) Molecular landscape (performed for n = 43 patients). RAS pathway: NRAS, KRAS, PTPN11, RIT1, CBL; Cohesin: RAD21, SMC1A, SMC3, STAG2; Spliceosome: SF3B1, SRSF2, U2AF1, ZRSR2. (C) Disease‐free survival and (D) overall survival according to the blast infiltration above (AML) or below (oligo‐AML) 20% among total BM nucleated cells (n = 41 patients receiving intensive chemotherapy for whom data were available).
Limiting the analysis to patients receiving intensive chemotherapy (n = 43/45) and available blast count (n = 41/43), the cutoff of 20% blasts among total BM nucleated cells had no impact on outcome. The 5y‐DFS and OS were 47.9% (95% CI: 30.4%–75.4%) and 72.4% (95% CI: 55.9%–93.9%) compared to 47.5% (95% CI: 28.6%–79.0%, p‐value = 0.98) and 72.9% (95% CI: 55.1%–96.4%; p‐value = 0.83) in patients with ≥ 20% blasts (AML) and < 20% blasts (oligo‐AML) respectively (Figure 1C,D). This suggests that the 20% BM blast cutoff is irrelevant in AEML. In this population of young adults with AEML, the presence of UBTF‐TD was associated with a decreased DFS compared to NPM1‐mutated patients and NPM1/UBTF‐unmutated patients although it did not reach statistical significance (5y‐DFS: 15% [95% CI: 2.8%–80.4%], 58.2% [95% CI: 37.4%–90.5%] and 66.7% [95% CI: 46.6%–95.3%] respectively; p = 0.12) (Figure S2).
3.3. NPM1 ‐Mutated AEML Molecular Features
Our cohort of AEML included 15 cases with NPM1 mutations, which represented the most frequent molecular lesion in young adults. The median BM blast infiltration was 20% and ranged from 6% (Figure 2A) to 40% of total BM nucleated cells. However, the median NPM1‐mutated cell fraction was 64% and ranged from 40% to100% of the BM cells, demonstrating that the mutation was not restricted to the blast compartment but was also present in differentiated myeloid cells (Figure S3).
FIGURE 2.
AEML with NPM1 mutations in young adults. (A) May‐Grünwald‐Giemsa‐stained bone marrow smear in a 40‐year‐old female patient with NPM1 mutation (VAF 46%). The complete blood count showed pancytopenia (WBC 4.6 × 109/L, hemoglobin 7.3 g/dL, platelets 89 × 109/L). The bone marrow (performed twice with reproducible results) showed 6% myeloid blasts with erythroid hyperplasia (72% erythroblasts) and dysmyelopoiesis. (B) Pattern of co‐mutations in NPM1‐mutated AML according to the FAB subtype. (C) Disease‐free survival and (D) overall survival in AEML/M6‐FAB AML with NPM1 mutation compared to non‐M6‐FAB AML with NPM1 mutations.
These cases were compared to 174 cases of NPM1‐mutated AML without AEML morphology enrolled in the ALFA‐0702 study. The cases were classified based on BM morphology following FAB criteria with a blast threshold of 20%. This cohort included 85 NPM1‐mutated AML with granulocytic (M1/M2) morphology and 96 NPM1‐mutated AMLs with monocytic (M4/M5) morphology. AML without differentiation (M0, n = 3) or not classified according to FAB were excluded from analyzes. The molecular landscape of the total cohort of NPM1‐mutated cases revealed a specific co‐mutational background associated with AEML (M6) morphology (Table S3). Compared to NPM1‐mutated M1/M2 and M4/M5‐AMLs, NPM1‐mutated M6‐AMLs were enriched in cohesin gene (47% vs. 16% and 18%, p‐value = 0.015) and WT1 mutations (40% vs. 11% and 6%, p‐value < 0.001) and depleted in FLT3‐ITDs (7% vs. 38% and 45%, p‐value = 0.017) and DNMT3A mutations (20% vs. 33% and 70%, p‐value = 0.032) (Figure 2B). Among NPM1‐mutated cases, the outcome of M6‐AMLs was not different from non‐M6‐AMLs. The 5y‐DFS and OS were 50.9% (95% CI: 30.5%–85.1%) and 72.0% (95% CI: 51.9%–99.8%) compared to 67.7% (95% CI: 61.0%–75.2%; p‐value = 0.34) and 69.9% (95% CI: 63.4%–77.1%; p‐value = 0.82) in patients with M6‐AML and non‐M6‐AML, respectively (Figure 2C,D). In addition, M4/M5 morphology was associated with a poorer prognosis than M1/M2 morphology. This was due to the over‐representation of poor prognosis “triple‐mutated” cases (i.e., NPM1 mut + DNMT3A mut + FLT3‐ITD) [16] in M4/M5‐AML (29/96; 30%) compared to M1/M2‐AML (12/85; 14%) (Figure S4).
4. Discussion
The diagnostic criteria for AEML have evolved through successive classifications of myeloid malignancies, and it is no longer recognized as a distinct entity in the latest WHO and ICC classifications. Our study aimed to investigate the biological coherence of AEML as defined by morphology, using contemporary genomic approaches, and to evaluate whether its distinctive morphologic presentation reflects an underlying, specific molecular signature.
In the present study, we used historical morphological criteria and showed that AEML has different molecular and cytogenetic characteristics depending on the age group. While complex karyotypes and TP53 mutations predominated in older adults (> 60 years), most younger adults (18–60 years, median age 42) had clinical de novo diseases and harbored high frequencies of normal karyotypes (65%) as well as specific molecular features. Using the current classification criteria proposed by the ICC and WHO in 2022 in our cohort of young adults with AEML, 56% (ICC) to 63% (WHO) are diagnosed with AML, and 27%–17% are classified as MDS/AML (ICC) or MDS‐IB2 (WHO).
Previous studies have shown that AEML shared similarities with MDS including myeloid dysplasia and a high frequency of TP53 mutations and adverse karyotypes [4, 5]. In the study by Hasserjian et al., two thirds of AEML patients had adverse karyotypes [5]. However, only 35% of patients had de novo AML, and the median age was 64 years, which could explain discrepancies with our results. Similarly, in the study by Grossman et al., the median age was 69 years. Complex karyotypes were found in 40% of AEML patients, and TP53 was the most frequent mutation in 43.5% of cases, followed by NPM1 mutations in 16.3% of patients [4]. Importantly, NPM1 correlated with lower age, whereas mutations in TP53 were correlated with higher age as observed in our cohort.
In our cohort, NPM1 mutations were found in 35% of young patients. Recent classifications emphasize the need to investigate NPM1 mutations in patients with less than 20% BM blasts, as NPM1‐mutated myeloid malignancies have been shown to benefit from AML‐type induction chemotherapy [17, 18]. The threshold of blasts required for the diagnosis of AML with an NPM1 mutation is therefore 10% according to the ICC [8], whereas the diagnosis of AML can be made regardless of the percentage of blasts in the presence of an NPM1 mutation according to the WHO [7]. Notably, among our 15 AEML with NPM1 mutations, 6 had less than 20% blasts, and 3 had less than 10% blasts in BM. Other recurrent alterations included UBTF‐TDs, which were recently described as recurrent in adult AML with dysplastic morphological features and poor prognosis [14, 19]. NPM1::MLF1 fusion and KMT2A‐PTD were each found in 3 cases and are known to be recurrent in patients with high‐risk MDS and AML [20, 21, 22, 23]. Together, these 4 mutually exclusive alterations (NPM1 mut, UBTF‐TD, NPM1::MLF1 and KMT2A‐PTD) accounted for 72% of AEML cases in young adults. Only 12% had complex karyotypes (all co‐occurring with TP53 mutations). WT1 mutations were also frequent (30% of cases), although not mutually exclusive of the preceding alterations. Notably, an association between WT1 mutations and M6 morphology has already been reported [24].
Additionally, while NPM1 mutations are recognized as defining a distinct AML entity with favorable prognosis [15], sequencing analyzes revealed specific patterns of co‐mutations associated with distinct morphologic subtypes. NPM1‐mutated cases with M6 morphology were enriched in WT1 and cohesin gene mutations and depleted in FLT3‐ITD and DNMT3A mutations. This is reminiscent of UBTF‐TD AML where the presence of FLT3‐ITD is associated with M1/M2 morphology while its absence is associated with M6 morphology [14]. This suggests that co‐occurring mutations may result in different blastic differentiation capacities and thus lead to different BM morphology and blastic infiltration. However, M6 morphology had no impact on outcomes in NPM1‐mutated cases.
In conclusion, this study highlights the enrichment of AML‐type aberrations in younger adults with a diagnosis of AEML and points to the relevance of including specific abnormalities, such as UBTF‐TD, in molecular screening panels in this context. In this age group, our findings support that morphologically defined AEML often corresponds to AML according to current genetic criteria, consistent with recent classification systems that prioritize molecular features over morphology.
Author Contributions
L.F., B.P., N.D., T.B. designed the study and wrote the paper. B.P., G.C., E.F., L.G., T.B. performed morphology. L.F., C.P., N.D., C.R.‐L., V.L. performed the molecular analyses and cytogenetics. C.H., C.P., N.D. supervised the management of the HDF‐AML observatory. K.C.‐L., M.H., H.D., R.I. provided clinical data and supervised the management of the ALFA‐0702 database. L.F., L.V., N.D. performed statistics. D.L., C.Be., A.C., C.Bo., B.C., S.T., K.J.‐W., J.P.‐M. provided clinical data.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Figure S1. Study flowchart.
Figure S2. Prognosis of M6‐FAB AML according to their molecular group. (A) Disease‐free survival. (B) Overall survival.
Figure S3. Measurement of blast infiltration and NPM1‐mutated cell fraction (CF) in bone marrow. The mutated CF represents twice the NPM1 mutation variant allele frequency in a heterozygous state.
Figure S4. Prognosis of NPM1‐mutated AML according to the FAB subtype in young adults receiving intensive chemotherapy. (A and C) Disease‐free survival. (B and D) Overall survival. TP: “triple positive” (DNMT3A mut + FLT3‐ITD + NPM1 mut).
Table S1. Patients characteristics.
Table S2. Assessment of dysmyelopoiesis.
Table S3. Co‐mutations in NPM1‐mutated AML according to FAB categorization.
Acknowledgments
The authors thank Christophe Roumier and the Tumor Bank of the Lille University Hospital for handling, conditioning, and storing patient samples. The work of all physicians and clinical research assistants is also acknowledged.
Funding: The authors received no specific funding for this work.
Laurène Fenwarth and Benjamin Podvin contributed equally as co‐first authors.
Nicolas Duployez and Thomas Boyer contributed equally as co‐last authors.
Contributor Information
Nicolas Duployez, Email: nicolas.duployez@chu-lille.fr.
Thomas Boyer, Email: boyer.thomas@chu-amiens.fr.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. Study flowchart.
Figure S2. Prognosis of M6‐FAB AML according to their molecular group. (A) Disease‐free survival. (B) Overall survival.
Figure S3. Measurement of blast infiltration and NPM1‐mutated cell fraction (CF) in bone marrow. The mutated CF represents twice the NPM1 mutation variant allele frequency in a heterozygous state.
Figure S4. Prognosis of NPM1‐mutated AML according to the FAB subtype in young adults receiving intensive chemotherapy. (A and C) Disease‐free survival. (B and D) Overall survival. TP: “triple positive” (DNMT3A mut + FLT3‐ITD + NPM1 mut).
Table S1. Patients characteristics.
Table S2. Assessment of dysmyelopoiesis.
Table S3. Co‐mutations in NPM1‐mutated AML according to FAB categorization.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.