<i>ASXL1</i>mutations in AML are associated with specific clinical and cytogenetic characteristics

Kakosaiou, Katerina; Panitsas, Fotios; Daraki, Aggeliki; Pagoni, Maria; Apostolou, Paraskevi; Ioannidou, Agapi; Vlachadami, Ioanna; Marinakis, Theodoros; Giatra, Chara; Vasilatou, Diamantina; Sambani, Constantina; Pappa, Vassiliki; Manola, Kalliopi N.

doi:10.1080/10428194.2018.1433298

Cited by 24 publications

(30 citation statements)

References 36 publications

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“…These loss‐of‐function mutations have been associated with different myeloid disorders, participating in leukemogenesis and, in general, contributing to a worse prognosis. The globally described frequency in AML is 10.8%‐14.5%, with the highest incidence being reported in AML‐MRC: 20.8%‐35% . The search for clinic‐biological characteristics associated with the presence of this mutation in AML has been attempted in some studies with variable results, partly possibly due to the very different patient cohorts evaluated .…”

Section: Discussionmentioning

confidence: 99%

“…The globally described frequency in AML is 10.8%‐14.5%, with the highest incidence being reported in AML‐MRC: 20.8%‐35% . The search for clinic‐biological characteristics associated with the presence of this mutation in AML has been attempted in some studies with variable results, partly possibly due to the very different patient cohorts evaluated . In this series, we focused on the study of ASXL1 mutations in patients with AML‐MRC defined according to the latest WHO update, namely excluding patients with NPM1 mutation and CEBPA biallelic mutation, as opposed to previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…Within the AML‐MRC, ASXL1 mutations are mainly associated with older age and a background of MDS/MDS‐MPN cases. Although this last association had been reported in some AML ASXL1+ series, other publications, focused on patients with AML‐MRC, had shown contradictory results . In MDS and CMML the presence of ASXL1 mutations have been associated with shorter transformation time to AML, which could partly support the association of this mutation with a history of MDS and MDS‐MPN.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to cytogenetics, the mutation in ASXL1 has previously been associated with the absence of cytogenetic abnormalities related to myelodysplasia and intermediate cytogenetic risk in patients with AML‐MRC . In addition, ASXL mutations have been associated with various abnormalities such as trisomy 8 and alterations on chromosome 11 in all AMLs . In our series, we confirmed an association of ASXL1 mutation with normal karyotype; up to 56% of patients with AML‐MRC displaying a normal karyotype are ASXL1+ .…”

Section: Discussionmentioning

confidence: 99%

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ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype

et al. 2020

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Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML-MRC and 46 controls with acute myeloid leukemia without other specifications (AML-NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated with ASXL1 mutational status. Mutated ASXL1 (ASXL1+) was observed in 31% of patients with AML-MRC compared to 4.3% in AML-NOS.Its presence in AML-MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/ MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow, myelomonocytic/monocytic morphological features and normal karyotype. ASXL1 mutation was not observed in patients with myelodysplastic syndrome-related cytogenetic abnormalities or TP53 mutations. Differences in terms of overall survival were found only in AML-MRC patients without prior MDS or MDS/ MPN and with intermediate-risk karyotype, having ASXL1+ patients a worst outcome than ASXL1−. We conclude that the ASXL1 mutation frequency is high in AML-MRC patients being its presence associated with specific characteristics including morphological signs of dysplasia. This association raises the possible role of ASXL1 as a surrogate marker in AML-MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML-MRC with intermediate-risk karyotype. K E Y W O R D S AML-MRC, ASXL1, myelodysplasia, myeloid leukemia 3638 | PRATS-MARTÍN eT Al.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype

et al. 2020

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“…The most common is in position G646. The incidence of ASXL1 mutations increases significantly with age and correlates with t (8;21), trisomy 8 (+8) and del(7q)/− 7 chromosomal aberrations [95,96]. Otherwise, ASXL1 mutations are frequently associated with other mutations, such as RUNX1 and IDH2, conferring poor prognosis, far less with FLT3 and NPM1 mutants [96,97].…”

Section: Asxl1 Mutationsmentioning

confidence: 99%

Landscape of Tumor Suppressor Mutations in Acute Myeloid Leukemia

Panuzzo

Signorino

Calabrese

et al. 2020

JCM

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Acute myeloid leukemia is mainly characterized by a complex and dynamic genomic instability. Next-generation sequencing has significantly improved the ability of diagnostic research to molecularly characterize and stratify patients. This detailed outcome allowed the discovery of new therapeutic targets and predictive biomarkers, which led to develop novel compounds (e.g., IDH 1 and 2 inhibitors), nowadays commonly used for the treatment of adult relapsed or refractory AML. In this review we summarize the most relevant mutations affecting tumor suppressor genes that contribute to the onset and progression of AML pathology. Epigenetic modifications (TET2, IDH1 and IDH2, DNMT3A, ASXL1, WT1, EZH2), DNA repair dysregulation (TP53, NPM1), cell cycle inhibition and deficiency in differentiation (NPM1, CEBPA, TP53 and GATA2) as a consequence of somatic mutations come out as key elements in acute myeloid leukemia and may contribute to relapse and resistance to therapies. Moreover, spliceosomal machinery mutations identified in the last years, even if in a small cohort of acute myeloid leukemia patients, suggested a new opportunity to exploit therapeutically. Targeting these cellular markers will be the main challenge in the near future in an attempt to eradicate leukemia stem cells.

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Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study

et al. 2021

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Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations.

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ASXL1mutations in AML are associated with specific clinical and cytogenetic characteristics

Cited by 24 publications

References 36 publications

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype

Landscape of Tumor Suppressor Mutations in Acute Myeloid Leukemia

Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study

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