Heterogeneous prognosis among KIT mutation types in adult acute myeloid leukemia patients with t(8;21)

Qin, Ya‐Zhen; Zhu, Hong‐Hu; Jiang, Qian; Xu, Lei; Jiang, Hao; Wang, Yu; Zhao, Xinyang; Liu, Yanrong; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1038/s41408-018-0116-1

Cited by 21 publications

(26 citation statements)

References 14 publications

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“…Overall, 52 patients received treatment and were followed up at our hospital. As we previously reported, induction therapy consisted of 1‐2 cycles of the “3 + 7” regimen or the homoharringtonine, aclarubicin, and cytarabine regimen for the 37 adult patients, and cytarabine, idarubicin, and etoposide were used for the 15 pediatric patients . Forty‐eight patients received consolidation therapy after achieving CR.…”

Section: Methodsmentioning

confidence: 99%

“…As we previously reported, cDNA was used to perform PCR to test for c‐KIT mutations in exons 17 and 8 …”

Section: Methodsmentioning

confidence: 99%

“…As we previously reported, induction therapy consisted of 1-2 cycles of the "3 + 7" regimen or the homoharringtonine, aclarubicin, and cytarabine regimen for the 37 adult patients, and cytarabine, idarubicin, and etoposide were used for the 15 pediatric patients. 6,7,28 Forty-eight patients received consolidation therapy after achieving CR. Among them, 36 received an intermediate-dose cytarabinebased chemotherapy only, and 12 received chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a human leukocyte antigen (HLA)-identical sibling (n = 9) or an HLA haplotype-matched relative (n = 3) in CR1.…”

Section: Patients and Treatmentmentioning

confidence: 99%

“…[4][5][6] In addition, c-KIT mutation was found to be the most prevalent mutation in t(8;21) AML and has been demonstrated to be related to poor outcomes by many studies. [7][8][9] However, the specificity and sensitivity of the current risk stratification are not perfect. Whether other parameters could complement the use of molecular markers needs to be evaluated in t(8;21) AML.…”

Section: Cd34+aldh+-h/mrd-h Status Independently Predicts Relapsementioning

confidence: 99%

“…Minimal residual disease (MRD) levels indicated by RUNX1-RUNX1T1 transcript levels as well as c-KIT mutations have been demonstrated to be strong prognostic factors in t (8;21) AML. [4][5][6][7][8][9] However, their risk predictions are not perfect, and other markers have yet to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

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High aldehyde dehydrogenase activity at diagnosis predicts relapse in patients with t(8;21) acute myeloid leukemia

et al. 2019

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Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Although the detection of minimal residual disease (MRD), which is indicated by RUNX1‐RUNX1T1 transcript levels, plays a key role in directing treatment, risk stratification needs to be improved, and other markers need to be assessed. A total of 66 t(8;21) AML patients were tested for aldehyde dehydrogenase (ALDH) activity by flow cytometry at diagnosis, and 52 patients were followed up for a median of 20 (1‐34) months. The median percentage of CD34+ALDH+, CD34+CD38‐ALDH+, and CD34+CD38+ALDH+ cells among nucleated cells were 0.028%, 0.012%, and 0.0070%, respectively. The CD34+ALDH+‐H, CD34+CD38‐ALDH+‐H, and CD34+CD38+ALDH+‐H statuses (the percentage of cells that were higher than the individual cutoffs) were all significantly associated with a lower 2‐year relapse‐free survival (RFS) rate in both the whole cohort and adult patients (P = .015, .016, and .049; P = .014, .018, and .032). Patients with < 3‐log reduction in the RUNX1‐RUNX1T1 transcript level after the second consolidation therapy (defined as MRD‐H) had a significantly lower 2‐year RFS rate than patients with ≥ 3‐log reduction (MRD‐L) (P = .017). The CD34+ALDH+ status at diagnosis was then combined with the MRD status. CD34+ALDH+‐L/MRD‐H patients had similar 2‐year RFS rates to both CD34+ALDH+‐L/MRD‐L and CD34+ALDH+‐H/MRD‐L patients (P = .50 and 1.0); and CD34+ALDH+‐H/MRD‐H patients had significantly lower 2‐year RFS rate compared with CD34+ALDH+‐L and/or MRD‐L patients (P < .0001). Multivariate analysis showed that CD34+ALDH+‐H/MRD‐H was an independent adverse prognostic factor for relapse. In conclusion, ALDH status at diagnosis may improve MRD‐based risk stratification in t(8;21) AML, and concurrent high levels of CD34+ALDH+ at diagnosis and MRD predict relapse.

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Section: Methodsmentioning

confidence: 99%

“…As we previously reported, cDNA was used to perform PCR to test for c‐KIT mutations in exons 17 and 8 …”

Section: Methodsmentioning

confidence: 99%

Section: Patients and Treatmentmentioning

confidence: 99%

Section: Cd34+aldh+-h/mrd-h Status Independently Predicts Relapsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High aldehyde dehydrogenase activity at diagnosis predicts relapse in patients with t(8;21) acute myeloid leukemia

et al. 2019

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Combination of KIT and FLT3‐ITD mutation status with minimal residual disease levels guides treatment strategy for adult patients with inv(16) acute myeloid leukemia in first complete remission

Wang

Dao

Wang

et al. 2022

Hematological Oncology

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Although several studies have investigated the benefits of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for patients with inv (16) acute myeloid leukemia (AML) in first complete remission (CR1) individually stratified by KIT or FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) mutation status or minimal residual disease (MRD) levels, evaluation based on the combination of mutation status and MRD levels remains absent. This study included 157 adult patients with inv (16) AML who were consecutively diagnosed and receiving treatment at our center. A total of 50 (31.6%) patients had KIT mutations (KITMU), and the risk of relapse was significantly higher in patients with KITMU than in patients with KITWT (p < 0.001). A total of 12 patients (7.6%) had FLT3‐ITD, and FLT3‐ITD+ tended to be related to a higher risk of relapse (p = 0.14). KITMU, FLT3‐ITD and MRD3‐H (beta subunit of core binding factor–myosin heavy chain 11 levels >0.2% after course 2 of consolidation therapy) were independent adverse prognostic factors for relapse with patients who received allo‐HSCT at CR1 were censored at the time of transplantation. After combination, patients were categorized into molecularly defined high‐risk (M‐HR; KITMU or FLT3‐ITD+ with MRD3‐H; n = 30), low‐risk (M‐LR; KITWT and FLT3‐ITD‐ with MRD3‐L; n = 45) and intermediate‐risk (M‐IR; others; n = 70) groups. For the M‐HR group, allo‐HSCT significantly improved both cumulative incidence of relapse cumulative incidence of relapse (CIR) and overall survival (OS) (11.1% vs. 92.6%, p < 0.001; 90.0% vs. 34.1%, p = 0.019). For the M‐IR group, allo‐HSCT significantly improved CIR but did not affect OS (14.1% vs. 62.2%, p = 0.0004; 73.3% vs. 68.3%, p = 0.43). For the M‐LR group, allo‐HSCT had no significant effect on both CIR and OS (0% vs. 35.1%, p = 0.31; 100% vs. 78.8%, p = 0.22). Therefore, the combination of KIT and FLT3‐ITD mutation status with MRD levels may identify inv (16) AML patients with high‐risk who can benefit from allo‐HSCT in CR1.

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Synthetic CXCR4 Antagonistic Peptide Assembling with Nanoscaled Micelles Combat Acute Myeloid Leukemia

Meng

Xing

et al. 2020

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Acute myeloid leukemia (AML) is the most common adult acute leukemia with very low survival rate due to drug resistance and high relapse rate. The C‐X‐C chemokine receptor 4 (CXCR4) is highly expressed by AML cells, actively mediating chemoresistance and reoccurrence. Herein, a chemically synthesized CXCR4 antagonistic peptide E5 is fabricated to micelle formulation (M‐E5) and applied to refractory AML mice, and its therapeutic effects and pharmacokinetics are investigated. Results show that M‐E5 can effectively block the surface CXCR4 in leukemic cells separated from bone marrow (BM) and spleen, and inhibit the C‐X‐C chemokine ligand 12‐mediated migration. Subcutaneous administration of M‐E5 significantly inhibits the engraftment of leukemic cells in spleen and BM, and mobilizes residue leukemic cells into peripheral blood, reducing organs’ burden and significantly prolonging the survival of AML mice. M‐E5 can also increase the efficacy of combining regime of homoharringtonine and doxorubicin. Ribonucleic acid sequencing demonstrates that the therapeutic effect is contributed by inhibiting proliferation and enhancing apoptosis and differentiation, all related to the CXCR4 signaling blockade. M‐E5 reaches the concentration peak at 2 h after administration with a half‐life of 14.5 h in blood. In conclusion, M‐E5 is a novel promising therapeutic candidate for refractory AML treatment.

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Heterogeneous prognosis among KIT mutation types in adult acute myeloid leukemia patients with t(8;21)

Cited by 21 publications

References 14 publications

High aldehyde dehydrogenase activity at diagnosis predicts relapse in patients with t(8;21) acute myeloid leukemia

High aldehyde dehydrogenase activity at diagnosis predicts relapse in patients with t(8;21) acute myeloid leukemia

Combination of KIT and FLT3‐ITD mutation status with minimal residual disease levels guides treatment strategy for adult patients with inv(16) acute myeloid leukemia in first complete remission

Synthetic CXCR4 Antagonistic Peptide Assembling with Nanoscaled Micelles Combat Acute Myeloid Leukemia

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