Erratum: Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

Madan,; Pavithra, S.; Han, Li; Mayakonda, Anand; Nagata, Yusuke; Sundaresan, Janani; Kanojia, Deepika; Yoshida, Kenichi; Ganesan, Saravanan; Hattori, Noritaka; Fulton, Noreen; Tan, Kah Wei; Alpermann, Tamara; Kuo, M. T.; Rostami, Shahrbano; Matthews, John; Sanada, Masashi; Liu, L; Shiraishi, Yuichi; Miyano, Satoru; Chendamarai, Ezhilarasi; Hou, H.-A.; Malnassy, Gregory; Ma, Turner; Garg, Monika; Ding, Lili; Sun, Qing; Chien, Wu Chien; Ikezoe, Takayuki; Lill, Michael; Biondi, Andrea; Larson, Richard A.; Powell, Bayard L.; Lübbert, Michael; Chng, Wee‐Joo; Tien, Hwei‐Fang; Heuser, Michael; Ganser, Arnold; Koren‐Michowitz, Maya; Kornblau, S.; Kantarjian, H.; Nowak, Daniel; Hofmann, W.-K.; Yang, Hongyong; Stock, Wendy; Ghavamzadeh, A; Haferlach, Torsten; Ogawa, Shozo; Shi-h, Liu; Mathews,; Koeffler, HP

doi:10.1038/leu.2016.237

Cited by 28 publications

(16 citation statements)

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“…An increased in the frequency of mutations was also noted in ARID1B and RUNX1 genes in relapse [40]. Additionally, other commonly known AML mutations such as NPM1 and DNMT3A are not seen in APL [40].…”

Section: Mutational Landscape Of Aplmentioning

confidence: 93%

“…The genetic alterations that occur in APL differ at diagnosis and at relapse. Mutations in PML and RARA proteins are common in relapse APL and are rarely seen at initial diagnosis [40]. An increased in the frequency of mutations was also noted in ARID1B and RUNX1 genes in relapse [40].…”

Section: Mutational Landscape Of Aplmentioning

confidence: 93%

“…Mutations in PML and RARA proteins are common in relapse APL and are rarely seen at initial diagnosis [40]. An increased in the frequency of mutations was also noted in ARID1B and RUNX1 genes in relapse [40]. Additionally, other commonly known AML mutations such as NPM1 and DNMT3A are not seen in APL [40].…”

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

“…Aside from the expression of the characteristic PML-RARA fusion protein, APL has a unique mutational landscape in regards to other somatic co-mutations. Recurrent mutations have also been noted in FLT3, WT1, NRAS, KRAS, ARID and PML genes [40]. The Fms like tyrosine kinase 3 (FMLT3) gene has been shown to be the most commonly mutated in primary APL [40].…”

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

“…Recurrent mutations have also been noted in FLT3, WT1, NRAS, KRAS, ARID and PML genes [40]. The Fms like tyrosine kinase 3 (FMLT3) gene has been shown to be the most commonly mutated in primary APL [40]. Non-silent mutations may provide a cooperative effect with the PML-RARA fusion in disease progression.…”

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

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Acute promyelocytic leukemia (APL): a review of the literature

et al. 2020

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Acute Promyelocytic Leukemia (APL) is characterized by a block in differentiation where leukemic cells are halted at the promyelocyte stage. A characteristic balanced chromosomal translocation between chromosomes 15 and 17 t (15;17) (q24; q21) is seen in 95% of cases-the translocation results in the formation of the PML-RARA fusion protein. The introduction of retinoic acid (RA) and arsenic trioxide (ATO) has been responsible for initially remarkable cure rates. However, relapsed APL, particularly in the high-risk subset of patients, remains an important clinical problem. In addition, despite the success of ATRA & ATO, many clinicians still elect to use cytotoxic chemotherapy in the treatment of APL. Patients who become resistant to ATO have an increased risk of mortality. The probability of relapse is significantly higher in the high-risk subset of patients undergoing treatment for APL; overall approximately 10-20% of APL patients relapse regardless of their risk stratification. Furthermore, 20-25% of patients undergoing treatment will develop differentiation syndrome, a common side effect of differentiation agents. Recent evidence using in vitro models has shown that mutations in the B2 domain of the PML protein, mediate arsenic resistance. Alternative agents and approaches considering these clinical outcomes are needed to address ATO resistance as well as the relapse rate in high risk APL.

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Section: Mutational Landscape Of Aplmentioning

confidence: 93%

Section: Mutational Landscape Of Aplmentioning

confidence: 93%

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

Section: Mutational Landscape Of Aplmentioning

confidence: 99%

See 3 more Smart Citations

Acute promyelocytic leukemia (APL): a review of the literature

et al. 2020

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A distinct immunophenotype identifies a subset of NPM1‐mutated AML with TET2 or IDH1/2 mutations and improved outcome

et al. 2018

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Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in AML. NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings. Of 84 cases (63%) that lacked monocytic differentiation ("myeloid AML"), 40 (48%) demonstrated an acute promyelocytic leukemia-like (APL-like) immunophenotype by flow cytometry, with absence of CD34 and HLA-DR and strong myeloperoxidase expression, in the absence of a PML-RARA translocation. Pathologic variants in TET2, IDH1, or IDH2 were identified in 39/40 APL-like cases. This subset of NPM1-mutated AML was associated with longer relapse-free and overall survival, when compared with cases that were positive for CD34 and/or HLA-DR. The combination of NPM1 and TET2 or IDH1/2 mutations along with an APL-like immunophenotype identifies a distinct subtype of AML. Further studies addressing its biology and clinical significance may be especially relevant in the era of IDH inhibitors and recent work showing efficacy of ATRA therapy in NPM1 and IDH1-mutated AML.

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Clonal evolution of acute myeloid leukemia from diagnosis to relapse

Vosberg

Greif

2019

Genes Chromosomes & Cancer

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Based on the individual genetic profile, acute myeloid leukemia (AML) patients are classified into clinically meaningful molecular subtypes. However, the mutational profile within these groups is highly heterogeneous and multiple AML subclones may exist in a single patient in parallel. Distinct alterations of single cells may be key factors in providing the fitness to survive in this highly competitive environment. Although the majority of AML patients initially respond to induction chemotherapy and achieve a complete remission, most patients will eventually relapse. These points toward an evolutionary process transforming treatment‐sensitive cells into treatment‐resistant cells. As described by Charles Darwin, evolution by natural selection is the selection of individuals that are optimally adapted to their environment, based on the random acquisition of heritable changes. By changing their mutational profile, AML cell populations are able to adapt to the new environment defined by chemotherapy treatment, ultimately leading to cell survival and regrowth. In this review, we will summarize the current knowledge about clonal evolution in AML, describe different models of clonal evolution, and provide the methodological background that allows the detection of clonal evolution in individual AML patients. During the last years, numerous studies have focused on delineating the molecular patterns that are associated with AML relapse, each focusing on a particular genetic subgroup of AML. Finally, we will review the results of these studies in the light of Darwinian evolution and discuss open questions regarding the molecular background of relapse development.

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Erratum: Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

Cited by 28 publications

References 0 publications

Acute promyelocytic leukemia (APL): a review of the literature

Acute promyelocytic leukemia (APL): a review of the literature

A distinct immunophenotype identifies a subset of NPM1‐mutated AML with TET2 or IDH1/2 mutations and improved outcome

Clonal evolution of acute myeloid leukemia from diagnosis to relapse

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