Correlation Analysis and Prognostic Impacts of Biological Characteristics in Elderly Patients with Acute Myeloid Leukemia

Abstract

Background The significant heterogeneity of elderly AML patients’ biological features has caused stratification difficulties and adverse prognosis. This paper did a correlation study between their genetic mutations, clinical features, and prognosis to further stratify them. Methods 90 newly diagnosed elderly acute myeloid leukemia (AML) patients (aged ≥60 years) who detected genetic mutations by next-generation sequencing (NGS) were enrolled between April 2015 and March 2021 in our medical center. Results A total of 29 genetic mutations were identified in 82 patients among 90 cases with a frequency of 91.1%. DNMT3A, BCOR, U2AF1, and BCORL1 mutations were unevenly distributed among different FAB classifications ( p < 0.05). DNMT3A, IDH2, NPM1, FLT3-ITD, ASXL1, IDH1, SRSF2, BCOR, NRAS, RUNX1, U2AF1, MPO, and WT1 mutations were distributed differently when an immunophenotype was expressed or not expressed ( p <0.05). NPM1 and FLT3-ITD had higher mutation frequencies in patients with normal chromosome karyotypes than abnormal chromosome karyotypes ( p <0.001, p =0.005). DNMT3A and NRAS mutations predicted lower CR rates. DNMT3A, TP53, and U2AF1 mutations were related to unfavorable OS. TET2 mutation with CD123+, CD11b+ or CD34- predicted lower CR rate. IDH2+/CD34- predicted lower CR rate. ASXL1+/CD38+ and SRSF2+/CD123- predicted shorter OS. Conclusion The study showed specific correlations between elderly AML patients’ genetic mutations and clinical features, some of which may impact prognosis.

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia

“…Of all the reported cytogenetic abnormalities, the most frequent were mutations involving NPM1 (7), FLT3 (7), and DNMT3A (6). Regarding immunophenotyping results, the most frequent immunophenotyping markers were CD34 (7), HLA-DR (5), CD45 (4), and CD13 (4) [69][70][71][72][73][74][75][76][77][78]. The NPM1 mutation was one of the most frequent genetic aberrations detected in the populations of the different studies (7/10), and it is indeed the most frequent in AML cases, usually representing a favorable prognosis when presented as a single mutation [14,[70][71][72][73][74][75]77].…”

“…Regarding immunophenotyping results, the most frequent immunophenotyping markers were CD34 (7), HLA-DR (5), CD45 (4), and CD13 (4) [69][70][71][72][73][74][75][76][77][78]. The NPM1 mutation was one of the most frequent genetic aberrations detected in the populations of the different studies (7/10), and it is indeed the most frequent in AML cases, usually representing a favorable prognosis when presented as a single mutation [14,[70][71][72][73][74][75]77]. However, as previously stated, these mutations can be commonly associated with mutations in other genes, such as DNMT3A, FLT3, TET2, IDH1, and IDH2, all of which directly influence AML leukemogenesis progression [71,76].…”

“…Biomedicines 2023, 10, x FOR PEER REVIEW 8 of 15 with increased expression of CD33 and/or CD123 and decreased expression or absence of CD13, HLA-DR, CD15, and CD64, along with CD34 [80,81]. Mutated FLT3 was reported in 7 of the 10 studies in Table 1 [70][71][72][73][74][75]77]. Although mutations may manifest as either internal tandem duplication of the juxta membrane domain (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3 TKD ), FLT3-ITD is the manifestation more highly associated with a worse prognosis in AML patients, predicting shorter remission and decreased OS [82,83].…”

“…In turn, the negative expression of HLA-DR is associated with a favorable evolution and The majority of studies in Table 1 (7/10) reported the presence of CD34+ immunophenotypic markers in most patients. Its presence is associated with immature cell populations, worse prognosis due to increased cell proliferation, blockage in differentiation, cell traffic and adhesion pathways, and increased resistance to induced apoptosis when compared with CD34-cells [69][70][71][75][76][77][78]. In a study by Loghavi et al [71], for example, it was demonstrated that CD34+ expression combined with a CD117 increase and a CD38 and/or HLA-DR decrease may characterize complications in AML.…”

“… Number of Patients Mean Age Immunophenotypic Characteristics Genetic Alterations References 41 (71% males and 29% females) 66 CD45, CD34, CD117, CD36, HLA-DR, CD13, CD33, CD7, CD71 Deletions involving chromosome 5/5q; deletions involving chromosome 7/7q; deletion of the TP53 locus (17p13) [ 69 ] 90 patients Aged > 60 years CD123, CD34, CD7, CD117, CD64, CD38, CD11b, CD33, CD56 TET2, DNMT3A, IDH2, NPM1, FLT3-ITD, CEBPA, ASXL1, IDH1, SRSF2, BCOR, TP53, NRAS, RUNX1, U2AF1, BCORL1, WT1, and FLT3-TKD. [ 70 ] 67 (26 males and 41 females) 64 (19–84) CD34, CD117, HLA-DR NPM1 p. W288fs DNMT3A, FLT3, TET2, IDH2, PTPN11, IDH1, NRAS, SRSF2, RAD21, WT1, ASXL1, and NF1 [ 71 ] 1040 (51.92% males and 48.08% females) 10.3 CD123 t(8;21), inv(16), CEBPA, NPM1, FLT3-ITD; monosomy 7, monosomy 5/del(5q), t(6;9) with DEK-NUP214 fusion, KMT2A rearrangements [ 72 ] 37 Males: 20 (54%), Females: 17 (46%) 54 (24–70) CD8+CD45RA− CD27+/int CD28+ PD1+ TCF1+ NPM1, DNMT3A, ASXL1, IDH2, TP53, CEBPA, NRAS, WT1 [ 73 ] 84 (51 females and 33 males) 65.5 (22–89) CD34-, HLA-DR-, CD117+, CD11b-, CD56+, CD13 …”