Mixed phenotype acute leukemia with PML-RARα positive: a case report and literature review

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Mixed phenotype acute leukemia (MPAL) is an uncommon type of leukemia. It is one kind of malignant clonal diseases that expresses more than one genealogical specific antigen simultaneously. Most MPAL patients are associated with clonal chromosomal abnormalities and molecular genetic changes, such as t(9;22) (q34;q11) and KMT2A (MLL) rearrangement. These specific abnormalities usually have important guiding significance in MPAL diagnosis, targeted therapy and prognosis judgment. In this paper, we reported a case of MPAL, T/myeloid (M5) with an unfrequent combination of PML-RARα positivity and t(15;17). The treatment was successful with chemotherapy for both AML and ALL with daunorubicin, cytarabine (DA) and vincristine, prednisone (VP). We reported here this suggestive MPAL case of rare disease condition and effective treatment, in order to provide experience for the early diagnosis and treatment of similar patients.

Related collections

Most cited references 21

Record: found
Abstract: found
Article: not found

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.

Daniel Arber, Attilio Orazi, Robert P. Hasserjian … (2016)

The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

0 comments Cited 2155 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia.

Klaus H. Metzeler, Tobias Herold, Maja Rothenberg-Thurley … (2016)

The clinical and prognostic relevance of many recently identified driver gene mutations in adult acute myeloid leukemia (AML) is poorly defined. We sequenced the coding regions or hotspot areas of 68 recurrently mutated genes in a cohort of 664 patients aged 18 to 86 years treated on 2 phase 3 trials of the German AML Cooperative Group (AMLCG). The median number of 4 mutations per patient varied according to cytogenetic subgroup, age, and history of previous hematologic disorder or antineoplastic therapy. We found patterns of significantly comutated driver genes suggesting functional synergism. Conversely, we identified 8 virtually nonoverlapping patient subgroups, jointly comprising 78% of AML patients, that are defined by mutually exclusive genetic alterations. These subgroups, likely representing distinct underlying pathways of leukemogenesis, show widely divergent outcomes. Furthermore, we provide detailed information on associations between gene mutations, clinical patient characteristics, and therapeutic outcomes in this large cohort of uniformly treated AML patients. In multivariate analyses including a comprehensive set of molecular and clinical variables, we identified DNMT3A and RUNX1 mutations as important predictors of shorter overall survival (OS) in AML patients <60 years, and particularly in those with intermediate-risk cytogenetics. NPM1 mutations in the absence of FLT3-ITD, mutated TP53, and biallelic CEBPA mutations were identified as important molecular prognosticators of OS irrespective of patient age. In summary, our study provides a comprehensive overview of the spectrum, clinical associations, and prognostic relevance of recurrent driver gene mutations in a large cohort representing a broad spectrum and age range of intensively treated AML patients.

0 comments Cited 215 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The genetic basis and cell of origin of mixed phenotype acute leukaemia

Dirk Reinhardt, Daisuke Tomizawa, Nobutaka Kiyokawa … (2018)

Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.

0 comments Cited 114 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Wanzhuo Xie: xiewanzhuo@zju.edu.cn

Journal

Journal ID (nlm-ta): Mol Cytogenet

Journal ID (iso-abbrev): Mol Cytogenet

Title: Molecular Cytogenetics

Publisher: BioMed Central (London )

ISSN (Electronic): 1755-8166

Publication date (Electronic): 11 February 2021

Publication date PMC-release: 11 February 2021

Publication date Collection: 2021

Volume: 14

Electronic Location Identifier: 10

Affiliations

GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Hematology, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; #79 Qingchun Road, Hangzhou, 310003 Zhejiang Province People’s Republic of China

Article

Publisher ID: 530

DOI: 10.1186/s13039-021-00530-9

PMC ID: 7879616

PubMed ID: 33573663

SO-VID: 7e277408-7aed-4f0d-b756-eb71a0f621d7

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 December 2020

Date accepted : 14 January 2021

Custom metadata

ScienceOpen disciplines: Genetics

Keywords: acute leukemia,t/myeloid subtype,mixed phenotype acute leukemia,pml-rarα,t(15;17),acute biphenotypic leukemia,case report

Data availability:

ScienceOpen disciplines: Genetics

Keywords: acute leukemia, t/myeloid subtype, mixed phenotype acute leukemia, pml-rarα, t(15;17), acute biphenotypic leukemia, case report

Mixed phenotype acute leukemia with PML-RARα positive: a case report and literature review

Read this article at

Abstract

Related collections

ScienceOpen Clinical Case Reports Collection

Most cited references 21

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.

Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia.

The genetic basis and cell of origin of mixed phenotype acute leukaemia

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 273

Cited by 3

Most referenced authors 434