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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 Oct;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

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas

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

Clin Lymphoma Myeloma Leuk 2015 Jun;15 Suppl:S85-90

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address:

Background: Acute myeloid leukemia (AML) with specific balanced 5q33 translocations are classified as AML with myelodysplasia-related changes regardless of their morphologic findings or antecedent hematologic disease, but the clinicopathologic features of such cases remain poorly understood.

Materials And Methods: From > 2000 cases of hematological malignancies seen at our institution between 2000 and 2013, we identified 9 AML patients with 5q33 translocations with variable partner loci, t(v;5q33).

Results: The study group included 8 men and 1 woman, with a median age of 64 years (range, 19-87 years). Read More

Leuk Res 2015 Oct 28;39(10):1034-40. Epub 2015 Jun 28.

Department of Pathology, Massachusetts General Hospital, United States. Electronic address:

The prognosis of acute myeloid leukemia (AML) is influenced by both disease-intrinsic and patient-related factors. In particular, AML following myelodysplastic syndrome (MDS) (AML with myelodysplasia-related changes, AML-MRC) has a poor prognosis. We hypothesized that patients with cytopenias prior to AML, but no known prior MDS, may share biologic features with AML-MRC. Read More

Am J Clin Pathol 2015 Jul;144(1):44-60

Massachusetts General Hospital, Boston, MA.

Objectives: At the 2013 Society for Hematopathology/European Association for Hematopathology Workshop, 36 cases were submitted to the session that covered acute erythroid leukemia (AEL), acute megakaryoblastic leukemia (AMKL), and reactive mimics.

Methods: Cases were reviewed by the session chairs and workshop panel to reach a consensus diagnosis.

Results: For acute erythroleukemia, erythroid/myeloid type, discussion acknowledged overlapping features between AEL and myelodysplastic syndromes. Read More

Am J Clin Pathol 2015 Jul;144(1):29-43

Department of Hematopathology, Mayo Clinic, Rochester, MN.

Objectives: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous disorder defined by morphologic, genetic, or clinical features. Genetic abnormalities associated with AML-MRC are often associated with adverse prognostic features, and many cases are preceded by a myelodysplastic syndrome (MDS) or a myelodysplastic/myeloproliferative neoplasm.

Methods: Although the criteria of 20% or more blasts in blood or bone marrow and multilineage dysplasia affecting 50% or more of cells in two or more of the myeloid lineages seem straightforward for AML-MRC, identification of morphologic dysplasia among observers is not always consistent, and there is morphologic overlap with other leukemic disorders such as acute erythroleukemia. Read More

Mod Pathol 2015 Jul 15;28(7):965-76. Epub 2015 May 15.

Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). Read More

Pathology 2015 Jun;47(4):289-93

1Diagnostic Haematology, Royal Melbourne Hospital 2University of Melbourne, Vic, Australia.

Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) with ≥50% erythroblasts comprise up to 5% of all cases of AML and 15% of MDS. The classification of these entities is currently fraught with difficulty and requires integration of clinical, morphological and cytogenetic features. The current World Health Organization classification of haematopoietic tumours recognises the entities of pure erythroid leukaemia and acute erythroid leukaemia (erythroid/myeloid), however, some cases of AML with erythroid predominance may also fulfil criteria for AML with myelodysplasia-related changes or therapy-related myeloid neoplasms. Read More

Clin Lymphoma Myeloma Leuk 2015 Jun 24;15(6):358-363. Epub 2014 Dec 24.

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Introduction: Sweet syndrome (SS) is associated with hematologic malignancies including acute myeloid leukemia (AML).

Patients And Methods: Records of patients with AML treated at our institution were reviewed to identify those with SS. Patient characteristics, laboratory values, and cytogenetic and molecular abnormalities were retrospectively reviewed. Read More

J Clin Pathol 2015 Mar 6;68(3):236-40. Epub 2015 Jan 6.

Department of Hematology/Oncology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, North Carolina, USA.

Aims: Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML. Read More

Hum Pathol 2015 Jan 2;46(1):65-73. Epub 2014 Oct 2.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in AML/MDS remains poorly characterized. Here, we report a series of 21 patients with myeloid neoplasms associated with MLL gene amplification from 1 institution. Read More

Br J Haematol 2014 Oct 8;167(1):80-6. Epub 2014 Jul 8.

Department of Paediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found 'AML with myelodysplasia-related changes' (AML-MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia-related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with 'AML, not otherwise specified' (AML-NOS), patients with 'AML-MRC' presented at a younger age, with a lower white blood cell count, higher incidence of 20-30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), NPM1 and CEBPA mutations. Read More

Am J Hematol 2014 Sep 19;89(9):874-81. Epub 2014 Jun 19.

Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.

We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML-MRC were analyzed and compared with those of AML not otherwise specified (AML-NOS). In all patients, 115 (25. Read More

Am J Hematol 2014 Oct 20;89(10):1010. Epub 2014 Jun 20.

Department of Haematology, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK; funded by the National Institute for Health Research, Richmond House, 79 Whitehall, London, SW1A 2NS, UK.

Eur J Haematol 2013 May 15;90(5):365-74. Epub 2013 Mar 15.

Division of Hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objectives: For patients with acute myeloid leukemia in first complete remission (AML CR1) lacking HLA-matched sibling donors (MSD), 8/8-matched unrelated donors (URD) are mostly used in cases with poor-risk features. For AML CR1 with intermediate cytogenetics, however, the benefit of 8/8-matched URD should be compared with non-allogeneic therapies as well as MSD.

Methods: To address this issue, we assessed the transplantation outcomes of 8/8-matched URD (n = 54) compared with MSD (n = 145) or autologous transplantation (n = 89) for AML CR1 with intermediate cytogenetics. Read More

Mod Pathol 2013 Jun 11;26(6):751-61. Epub 2013 Jan 11.

Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. Read More

Am J Clin Pathol 2012 Mar;137(3):395-402

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.

Acute promyelocytic leukemia (APL) is a relatively common form of acute myeloid leukemia (AML) that has an excellent prognosis. In contrast, secondary acute myeloid leukemias, including therapy-related AML and AML with myelodysplasia-related changes, have a relatively poor prognosis. We identified 9 cases of APL at our institution in which there was a history of chemotherapy, radiotherapy, chronic immunosuppression, or antecedent myelodysplastic syndrome. Read More

Hum Pathol 2012 Feb 9;43(2):153-64. Epub 2011 Dec 9.

Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Prominent erythroid proliferations (in which erythroid elements comprise ≥50% of total bone marrow cells) can be seen in various hematopoietic stem cell neoplasms. The myeloproliferative neoplasm polycythemia vera exhibits effective, overexuberant erythropoiesis resulting in an increased red blood cell mass; in contrast, most other diseases characterized by erythroid predominance exhibit ineffective hemopoiesis. The latter include acute erythroid leukemia (erythroid-myeloid and pure erythroid leukemia subtypes) as well as some cases of myelodysplastic syndromes, acute myeloid leukemia with myelodysplasia-related changes, and therapy-related myeloid neoplasms. Read More

J Pediatr Hematol Oncol 2011 Oct;33(7):e289-95

Department of Genetics, Cytogenetics Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

We report a unique pediatric case of hypergranular acute myeloid leukemia with myelodysplasia-related changes. The patient presented with moderate leukocytosis with neutrophilia with left-shift maturation and dysplasia, anemia, and multiple sclerotic bone lesions. The bone marrow was hypercellular with a predominance of myeloblast cells and/or abnormal promyelocytes with hypergranular cytoplasm. Read More

Br J Haematol 2011 Jul 9;154(2):185-95. Epub 2011 May 9.

Department of Paediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.

Advanced myelodysplastic syndrome (MDS) in children includes refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T) according to the paediatric modification of the World Health Organization classification. Clinical features and cytogenetics are essential to make a diagnosis because blast count alone is insufficient to differentiate MDS from acute myeloid leukaemia (AML). Little is known about molecular genetics in paediatric MDS but hypermethylation seem to be frequent. Read More

Surg Pathol Clin 2010 Dec 27;3(4):1153-64. Epub 2010 Nov 27.

Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive L235, Stanford, CA 94305, USA. Electronic address:

Acute myeloid leukemia (AML) with multilineage dysplasia was introduced in the 2001 World Health Organization (WHO) classification to encompass cases of AML characterized by myelodysplastic syndrome-like features. The 2008 WHO classification revised this group into a new category, AML with myelodysplasia-related changes (AML-MRC). The category now includes patients with at least 20% blasts in peripheral blood or bone marrow and any of the following: (1) AML arising from a previous MDS or mixed MDS/myeloproliferative neoplasm, (2) AML with a specific MDS-associated cytogenetic abnormality and/or (3) AML with multilineage dysplasia. Read More

Mod Pathol 2011 Mar 19;24(3):375-83. Epub 2010 Nov 19.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.

Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Read More

Arch Pathol Lab Med 2010 Sep;134(9):1261-70

Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Context: Acute erythroid leukemia (AEL) is an uncommon type of acute myeloid leukemia (AML), representing less than 5% of all cases. Acute erythroid leukemia is characterized by a predominant erythroid proliferation, and in the current World Health Organization (WHO) classification scheme there are 2 subtypes: erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia. Morphologic findings are most important for establishing the diagnosis. Read More

Arch Pathol Lab Med 2010 Aug;134(8):1143-51

Department of Pathology, United Hospital, St Paul, MN 55102, USA.

Context: Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3) adversely impact relapse risk after chemotherapy in patients with acute myeloid leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse, suggesting a potential role in chemoresistance, yet few reports have addressed the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML.

Objectives: To determine FLT3 mutations at diagnosis and relapse in a cohort of adult patients with chemoresistant AML and to correlate mutation status with multiple variables. Read More

Lancet Oncol 2010 Jun 5;11(6):543-52. Epub 2010 May 5.

Department of Oncology, St Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis, TN 38105-2794, USA.

Background: We sought to improve outcome in patients with childhood acute myeloid leukaemia (AML) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic cells and measurements of minimal residual disease (MRD) done by flow cytometry during treatment.

Methods: From Oct 13, 2002, to June 19, 2008, 232 patients with de-novo AML (n=206), therapy-related or myelodysplasia-related AML (n=12), or mixed-lineage leukaemia (n=14) were enrolled at eight centres. 230 patients were assigned by block, non-blinded randomisation, stratified by cytogenetic or morphological subtype, to high-dose (18 g/m(2), n=113) or low-dose (2 g/m(2), n=117) cytarabine given with daunorubicin and etoposide (ADE; induction 1). Read More

Leukemia 2010 Apr 14;24(4):740-7. Epub 2010 Jan 14.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.

Trisomy 11 in myelodysplastic syndromes (MDS) is rare, with undefined clinical significance and is currently assigned to the International Prognostic Scoring System (IPSS) intermediate-risk group. Over a 15-year period, we identified 17 MDS patients with trisomy 11 either as a sole abnormality (n=10) or associated with one or two additional alterations (n=7), comprising 0.3% of all MDS cases reviewed. Read More

Blood 2009 Feb 8;113(9):1906-8. Epub 2009 Jan 8.

Department of Pathology, Center for Clinical Investigation, Stanford University Medical Center, CA 94305, USA.

Although some studies have validated the 2001 World Health Organization (WHO) classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification has expanded this category into "AML with myelodysplasia-related changes" (AML-MRC). We evaluated the clinical, pathologic, cytogenetic, and molecular features of 100 AML patients using the 2008 WHO criteria. Read More