Newly diagnosed isolated myeloid sarcoma–paired NGS panel analysis of extramedullary tumor and bone marrow

Engel, Nils W.; Reinert, Jochim; Borchert, Nora; Panagiota, Victoria; Gabdoulline, Razif; Thol, Felicitas; Heuser, Michael; Fiedler, Walter

doi:10.1007/s00277-020-04313-x

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…Molecular alterations in myeloid sarcoma and concurrent bone marrow disease are concordant in ~70% of patients, suggesting that myeloid sarcoma may be derived from a common haematopoietic stem cell or precursor [ 68 , 69 ]. Relevant gene mutations are detected in a subset of patients with morphologically normal-appearing bone marrow, suggesting low-level clonal myeloid disease or CH in the bone marrow [ 68 , 70 ].…”

Section: Acute Myeloid Leukaemiamentioning

confidence: 99%

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

et al. 2022

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The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

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Section: Acute Myeloid Leukaemiamentioning

confidence: 99%

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

et al. 2022

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“…9), the blast may express CD11c, CD14, CD33, CD34, CD43, CD45, CD68, CD117, CD163, E-cadherin, GLUT1, glycophorin A, hemoglobin, IRF8, LMO2, lysozyme, myeloperoxidase, mutant CALR or NPM1, PU1, etc. [85, 85. A complex karyotype and FLT3, IDH1, IDH2, and NPM1and, particularly in cases representing progression of a prior MN, TP53 mutationshave been reported [94][95][96]. MS with erythroblastic differentiation are rare and more frequently seen de novo in young patients [93].…”

Section: Development Of Msmentioning

confidence: 99%

“…[85, 88–93]. A complex karyotype and FLT3 , IDH1 , IDH2 , and NPM1 – and, particularly in cases representing progression of a prior MN, TP53 mutations – have been reported [94–96]. MS with erythroblastic differentiation are rare and more frequently seen de novo in young patients [93].…”

Section: Development Of Msmentioning

confidence: 99%

Progression in Myeloid Neoplasms: Beyond the Myeloblast

Faria

Tzankov

2023

Pathobiology

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Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.

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“…For NGS-MRD analyses, bioinformatic analysis was performed using a sensitive error-corrected amplicon sequencing approach, which had a sensitivity threshold of 0.015%, to validate identified variants [10,12].…”

Section: Bioinformatics and Statistical Analysesmentioning

confidence: 99%

Molecular response patterns in relapsed/refractory AML patients treated with selinexor and chemotherapy

et al. 2022

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Relapse in patients with acute myeloid leukemia (AML) is common and is associated with a dismal prognosis. Treatment options are limited and the understanding of molecular response patterns is still challenging. We analyzed the clonal response patterns of 15 patients with relapsed/refractory AML treated with selinexor in a phase II trial (SAIL). DNA was analyzed at three time points and showed a decline of mutated alleles in FLT3, SF3B1, and TP53 under SAIL treatment. Overall survival (OS) was similar between patients with declining versus persisting clones. We show an interesting long-term course of a patient who relapsed after allogeneic stem cell transplantation (alloHCT) with SF3B1- and SRSF2-mutated AML and received selinexor as maintenance treatment for 4 years. Measurable residual disease (MRD) remained detectable for 2 weeks after donor lymphocyte infusion (DLI) in this patient and then remained negative under selinexor maintenance treatment. Selinexor was tolerated well and was stopped after 4 years of SAIL treatment. We present an exploratory study and identify subclonal patterns of patients treated with selinexor.

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Newly diagnosed isolated myeloid sarcoma–paired NGS panel analysis of extramedullary tumor and bone marrow

Cited by 11 publications

References 18 publications

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Progression in Myeloid Neoplasms: Beyond the Myeloblast

Molecular response patterns in relapsed/refractory AML patients treated with selinexor and chemotherapy

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