Search Our Scientific Publications & Authors

Leuk Res 2022 Jul 22;118:106869. Epub 2022 May 22.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Haematology, University Health Network, Toronto, ON, Canada. Electronic address:

Background: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a prognostically diverse disease. Owing to its favourable prognosis, AML-MRC with mutated NPM1 (NPM1) diagnosed on the basis of multi-lineage dysplasia has been reclassified into "AML with mutated NPM1". However, it remains unclear if NPM1 AML with antecedent MDS or MDS/MPN (AML-MRC-H) should also be reclassified into this subentity. Read More

Am J Clin Pathol 2022 05;157(5):691-700

Hematology, Beijing, China.

Objectives: To explore the distinct mutation profiles between acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and de novo AML and their relationships with prognosis.

Methods: Next-generation sequencing of 42 myeloid neoplasm-related genes in 293 newly diagnosed patients with AML.

Results: Eighty-four patients had AML-MRC, and 161 patients had de novo AML. Read More

J Cell Mol Med 2021 10 7;25(20):9557-9566. Epub 2021 Sep 7.

Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, Paris, France.

Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56-88). Read More

Int J Lab Hematol 2021 Jul;43 Suppl 1:78-81

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Philadelphia (BCR-ABL)-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN can transform into an accelerated or a blast phase, which is associated with poor response to standard therapy and low overall median survival. We present an interesting case of a patient with a history of PMF and progression and summarize the current studies on genetic features of myeloproliferative neoplasms in blast phase (MPN-BP) with an emphasis on PMF. Read More

Leuk Lymphoma 2021 10 27;62(10):2466-2474. Epub 2021 Apr 27.

Department of Hematology, Chinese PLA General Hospital, Beijing, China.

Double minute chromosomes (DMs) are rare in hematologic malignancies. We presented the cytogenetic characteristics and clinical features of the largest single-center cohort of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients with DMs. A total of 2576 AML patients and 1642 MDS patients were investigated, and 30 patients (AML = 19; MDS = 11) who had DMs were followed up. Read More

Cancers (Basel) 2021 Mar 11;13(6). Epub 2021 Mar 11.

Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Recent genetic studies on large patient cohorts with acute myeloid leukemia (AML) have cataloged a comprehensive list of driver mutations, resulting in the classification of AML into distinct genomic subgroups. Among these subgroups, chromatin-spliceosome (CS)-AML is characterized by mutations in the spliceosome, cohesin complex, transcription factors, and chromatin modifiers. Class-defining mutations of CS-AML are also frequently identified in myelodysplastic syndrome (MDS) and secondary AML, indicating the molecular similarity among these diseases. Read More

Zhongguo Dang Dai Er Ke Za Zhi 2021 Mar;23(3):271-278

Institute of Hematology&Blood Disease Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/State Key Laboratory of Experimental Hematology/National Clinical Research Center for Blood Diseases, Tianjin 300020, China.

Objective: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).

Methods: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis.

Results: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8. Read More

Cancers (Basel) 2020 Oct 30;12(11). Epub 2020 Oct 30.

Struttura Operativa Dipartimentale Ematologia, Azienda Ospedaliero-Universitaria Careggi, 50134 Firenze, Italy.

Acute myeloid leukemia (AML) "with myelodysplasia-related changes (MRC)" is considered a separate entity by the World Health Organization (WHO) classification of myeloid neoplasms. While anamnestic and cytogenetic criteria provide objective attribution to this subset, with clear unfavorable prognostic significance, the actual role of multi-lineage dysplasia (MLD) as assessed by morphology is debated. The aim of our work was to study MLD by a technique alternative to morphology, which is multiparameter flow cytometry (MFC), in a large series of 302 AML patients intensively treated at our Center. Read More

Am J Clin Pathol 2020 11;154(6):731-741

Department of Medicine, Duke University School of Medicine, Durham, NC.

Objectives: Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) represents a high-risk and somewhat diverse subtype of AML, and substantial confusion exists about the pathologic evaluation needed for diagnosis, which can include the patient's clinical history, cytogenetic analysis, mutational analysis, and/or morphologic evaluation. Treatment decisions based on incomplete or untimely pathology reports may result in the suboptimal treatment of patients with AML-MRC.

Methods: Using a PubMed search, diagnosis of and treatment options for AML-MRC were investigated. Read More

Cancer Cell 2020 09 9;38(3):380-399.e13. Epub 2020 Jul 9.

Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center (HUH CCC), 00029 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki (UH), 00029 Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland. Electronic address:

Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-γ response in lymphoma. Read More

Zhongguo Dang Dai Er Ke Za Zhi 2020 May;22(5):460-465

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

Objective: To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation.

Methods: Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed.

Results: Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). Read More

Cancer Med 2020 06 26;9(11):3637-3646. Epub 2020 Mar 26.

Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CISC/CIBERONC), Universidad de Sevilla, Sevilla, Spain.

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. Read More

Hum Pathol 2020 04 21;98:22-31. Epub 2020 Feb 21.

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. Electronic address:

Chromothripsis is a unique type of genomic instability and is recognized in various cancers. In myeloid neoplasms (MNs), chromothripsis was linked to poor prognosis and specific genetic alterations (complex karyotype, 5q deletions, and loss of TP53). However, the clinicopathologic features of MNs with chromothripsis have not been thoroughly characterized. Read More

Cancer Genet 2019 09 12;237:63-68. Epub 2019 Jun 12.

Department of Biology, University of Bari, Via Orabona 4, 70125 Bari, Italy.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous hematological disorder defined by morphological, genetic, and clinical features. Patients with AML-MRC often show cytogenetic changes, which are associated with poor prognosis. Straightforward criteria for AML-MRC diagnosis and a more rigorous characterization of the genetic abnormalities accompanying this disease are needed. Read More

Zhonghua Xue Ye Xue Za Zhi 2019 Jun;40(6):477-483

Pediatric Blood Diseases Centre, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China; State Key Laboratory of Experimental Hematology, Tianjin 300020, China.

To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) . Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. Read More

Cancer Med 2019 Sep 19;8(11):5108-5115. Epub 2019 Jul 19.

Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

In acute myeloid leukemia (AML), myelodysplasia-related changes contribute to a poor prognosis. This retrospective, propensity score-matched study analyzed 108 newly diagnosed AML patients with features of myelodysplasia syndrome (MDS) (aged 14-60 years) from 2014 to 2018, who received either idarubicin and cytarabine (IA) or decitabine, idarubicin and cytarabine (DAC+IA), and compared efficacy and toxicity between the two regimens. After propensity score matching, there were 54 patients in each group. Read More

Hum Pathol 2019 08 8;90:80-96. Epub 2019 May 8.

Department of Pathology and Laboratory Medicine, Pennsylvania State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, PA 17033. Electronic address:

The 2016/2017 World Health Organization (WHO) classification for acute myeloid leukemia (AML) includes new entities with gene mutations in NPM1 (AML-NPM1) and biallelic CEBPA (AML-biCEBPA). To retrospectively identify and study these new molecularly defined WHOentities, we reviewed clinicopathologic data and pretherapy archived pathologic materials at diagnosis for 143 consecutive AML cases (55.2% male, median age 62 [range 18-89] years) and classified all cases by the 2008 WHO (WHO) and revised WHO criteria. Read More

Semin Hematol 2019 04 22;56(2):90-95. Epub 2018 Aug 22.

Department of Pathology, University of Chicago, Chicago, IL. Electronic address:

In 2016 a revision of the World Health Organization (WHO) classification of acute myeloid leukemia (AML) was introduced that included changes to several disease categories. The WHO approach results in disease categories that are defined by a combination of clinical, morphologic, immunophenotypic, and genetic features in an attempt to define clinically relevant, biologic entities. This review summarizes the WHO approach as well as the priority of specific features for disease classification. Read More

Ann Hematol 2019 Mar 21;98(3):541-559. Epub 2019 Jan 21.

Department of Pharmacy Services and Clinical Sciences, Michigan Medicine and University of Michigan College of Pharmacy, 1540 E. Hospital Drive, Room CW 7-251B, Ann Arbor, MI, 48109-2054, USA.

Secondary AML is associated with a disproportionately poor prognosis, consistently shown to exhibit inferior response rates, event-free survival, and overall survival in comparison with de novo AML. Secondary AML may arise from the evolution of an antecedent hematologic disorder, or it may arise as a complication of prior cytotoxic chemotherapy or radiation therapy in the case of therapy-related AML. Because of the high frequency of poor-risk cytogenetics and high-risk molecular features, such as alterations in TP53, leukemic clones are often inherently chemoresistant. Read More

Blood Adv 2018 10;2(19):2513-2521

Department of Hematology/Oncology, Research Hospital, Institute of Medical Science.

Acute myeloid leukemia (AML) is a clonal myeloid neoplasm that typically arises de novo; however, some cases evolve from a preleukemic state, such as myelodysplastic syndrome (MDS). Such secondary AMLs and those with typical MDS-related clinical features are known as AMLs with myelodysplasia-related changes (AML-MRC). Because patients with AML-MRC have poor prognosis, more accurate diagnostic approaches are required. Read More

Mod Pathol 2018 06 5;31(6):873-880. Epub 2018 Feb 5.

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.

The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. Read More

Leuk Res 2017 10 25;61:39-43. Epub 2017 Aug 25.

Department of Laboratory Hematology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada. Electronic address:

In the recent update of WHO classification, the definition of myeloid neoplasms with erythroid predominance has been modified shifting the main criteria for calculating blast percentage from non-erythroid cells (NEC) to all nucleated marrow cells (ANC). Thus, the cases previously classified as erythroid/myeloid subtype of acute erythroid leukemia (AEL) based on the 2008 WHO will now be categorized either as myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia, not otherwise specified (AML-NOS). However, the clinical significance of this new classification has not been demonstrated. Read More

Mediterr J Hematol Infect Dis 2017 1;9(1):e2017045. Epub 2017 Jul 1.

Hematology, Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.

In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of and genes. The clinical course of this entity is often similar to MDS with 10-19% BM-blasts. Read More

J Natl Compr Canc Netw 2017 06;15(6):790-796

V617F mutation (mut) in acute myeloid leukemia (AML) is rare. We describe the clinicopathologic findings of a single-institution series of 11 de novo AML cases with V617. We identified cases of de novo AML with V617F over a 10-year period. Read More

Oncotarget 2017 May;8(18):29887-29905

Penn State Hershey Cancer Institute and Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania, USA.

Previous studies have linked increased frequency of glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency with genomic instability and the risk of carcinogenesis. However, the underlying mechanism is still not clear. A randomForest analysis of the gene expression array data from 55 MDS patients (GSE4619) demonstrated a significant (p = 0. Read More

Cancer Genet 2016 Jul-Aug;209(7-8):313-20. Epub 2016 May 27.

Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. Electronic address:

Double minute chromosomes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Dmin are rare in myeloid neoplasms and are generally associated with a poor prognosis. Most studies of dmin in myeloid neoplasms are case reports or small series. Read More

Ann Hematol 2016 Aug 14;95(8):1211-21. Epub 2016 Jun 14.

Dept. of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.

BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. Read More

Ann Lab Med 2016 Jul;36(4):377-9

Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.

Haematologica 2016 06 24;101(6):707-16. Epub 2016 Mar 24.

CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic

GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. Read More

Hematol Oncol 2017 Dec 7;35(4):894-899. Epub 2016 Mar 7.

Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.

Ring 21 is an unstable structural abnormality of chromosome 21 that can lead to RUNX1 gene amplification. We present a unique case with a carrier patient of a constitutional ring chromosome 21 (partial monosomy and trisomy 21) with dysmorphic features and congenital malformations phenotype, who developed acute myeloid leukaemia with myelodysplasia-related changes and two ring 21 chromosomes with RUNX1 amplification. The patient's constitutional ring 21 chromosome showed alterations in tumour suppressor genes, and oncogenes, but not in RUNX1. Read More