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Katsuya Yamamoto, Shinichiro Kawamoto, Yu Mizutani, Kimikazu Yakushijin, Tomoe Yamashita, Yuji Nakamachi, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami
The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality...
September 9, 2016: Cytogenetic and Genome Research
Keisuke Otsubo, Miharu Yabe, Hiromasa Yabe, Akiko Fukumura, Tsuyoshi Morimoto, Masahiko Kato, Hiroyuki Mochizuki
Mixed-phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B-lymphoid markers...
August 31, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
Hyeong Nyeon Kim, Mina Hur, Hanah Kim, Misuk Ji, Hee-Won Moon, Yeo-Min Yun, Mark Hong Lee
Mixed phenotype acute leukemia (MPAL) includes biphenotypic leukemia, bilineal leukemia, or its combination by the 2008 WHO classification. A few cases of combined biphenotypic/bilineal MPAL have been reported so far; they all had biphenotypic expressions in only one of the two distinct leukemic populations. A 43-year-old female presented with leukocytosis and bicytopenia. Her complete blood counts were: hemoglobin, 6.9 g/dL; white blood cells, 62.8×10(9)/L; and platelets, 83×10(9)/L. Neither lymphadenopathy nor organomegaly was observed...
July 2016: Annals of Clinical and Laboratory Science
Olive S Eckstein, Linghua Wang, Jyotinder N Punia, Steven M Kornblau, Michael Andreeff, David A Wheeler, Margaret A Goodell, Rachel E Rau
Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of poor-prognosis leukemias with immunophenotypic features of at least two cell lineages. The full spectrum of genetic mutations in this rare disease has not been elucidated, limiting our understanding of disease pathogenesis and our ability to devise targeted therapeutic strategies. Here, we sought to define the mutational landscape of MPAL by performing whole-exome sequencing on samples from 23 adult and pediatric MPAL patients. We identified frequent mutations of epigenetic modifiers, most notably mutations of DNMT3A, in 33% of adult MPAL patients...
August 2016: Experimental Hematology
Hiroyuki Takata, Taichi Ikebe, Hitohiro Sasaki, Yasuhiko Miyazaki, Eiichi Ohtsuka, Yoshio Saburi, Masao Ogata, Kuniaki Shirao
Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown...
2016: Internal Medicine
Jun Amaki, Hiromichi Matsushita, Yuka Kitamura, Ryoko Nagao, Hiromichi Murayama, Minoru Kojima, Kiyoshi Ando
We experienced the case of a 56-year-old male with B-lymphoid/myeloid lineage mixed phenotype acute leukemia (MPAL). A cytogenetic analysis of the patient's bone marrow revealed a complex karyotype, including der(9)t(7;9)(q11.2;p13). We identified an aberrant PAX5 transcript, including the exons 1A to 5 and the contiguous intron 5/6 sequence using the 3' rapid amplification of cDNA ends-polymerase chain reaction method, and confirmed their expression in the leukemic cells. Our case suggests that der(9)t(7;9)(q11...
2016: Leukemia Research Reports
Hong Tian, Yang Xu, Liming Liu, Lingzhi Yan, Zhengming Jin, Xiaowen Tang, Yue Han, Zhengzheng Fu, Huiying Qiu, Aining Sun, Depei Wu
The optimal treatment approach for mixed phenotype acute leukemia (MPAL) remains unknown, and prognostic factors for treatment outcomes need to be identified. In this study, 66 patients diagnosed with MPAL according to criteria published by the WHO in 2008 were retrospectively assessed to evaluate the effectiveness of treatment and identify predictive variables. Five patients died of severe infection after the first induction chemotherapy, 29 received alloHSCT after induction (HSCT group), and 32 received only chemotherapy (chemotherapy group)...
June 2016: Leukemia Research
Evans Roberts, Melody Oncale, Hana Safah, John Schmieg
Mixed-phenotype acute leukemia is a rare form of leukemia that is associated with a poor prognosis. Most cases of mixed-phenotype acute leukemia are de novo. However, therapy-related mixed-phenotype acute leukemia can occur, and are often associated with exposure to topoisomerase-II inhibitors and alkylating agents. There are no known treatment guidelines for therapy-related mixed-phenotype acute leukemia. We present a patient with T/myeloid mixed-phenotype acute leukemia secondary to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma...
January 2016: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
Reinhold Munker, Ruta Brazauskas, Hai Lin Wang, Marcos de Lima, Hanna J Khoury, Robert Peter Gale, Richard T Maziarz, Brenda M Sandmaier, Daniel Weisdorf, Wael Saber
Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68)...
June 2016: Biology of Blood and Marrow Transplantation
Samah A Kohla, Ahmad Al Sabbagh, Halima El Omri, Firyal A Ibrahim, Ivone B Otazu, Hessa Alhajri, Mohamed A Yassin
Mixed phenotype acute leukemia (MPAL) is considered as a rare type of leukemia with an incidence of less than 4% of all acute leukemia based on the most recent 2008 WHO classification. Common subtypes are the B/myeloid and T/myeloid; B/T and trilineage MPAL being extremely rare. We present a case of a male in his 20s, whose peripheral blood smears showed 34% blast cells and bone marrow with 70% blasts. Immunophenotyping by multiparametric flow cytometry showed two populations of blasts, the major one with B-lineage and the minor one with T-lineage...
2015: Clinical Medicine Insights. Blood Disorders
Anna Porwit, Marie C Béné
OBJECTIVES: This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. METHODS: We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. RESULTS: Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated...
September 2015: American Journal of Clinical Pathology
Limin Liu, Qi Qu, Wenjing Jiao, Yanming Zhang, Xiaoli Li, Chao Ding, Depei Wu
We treated 60 relapsed/refractory mixed-phenotype acute leukemia patients (MPAL-1) with increasing the aclarubicin dose in CAG regimen (HD-CAG, cytarabine (10 mg/m(2)/12 h, days 1-14), aclarubicin (5-7 mg/m(2)/day, days 1-14), granulocyte colony-stimulating factor (200 μg/m(2)/day, days 1-14). This was compared to 64 relapsed/refractory MPAL patients (MPAL-2) treated with DOAP regimen (daunorubicin, vincristine/vindesine, cytarabine and prednisone), 113 relapsed/refractory acute myeloid leukemia (AML) patients and 78 acute lymphocytic leukemia (ALL) patients treated with HD-CAG regimen...
August 2015: Leukemia Research
Bingjie Ding, Lanlan Zhou, Xuejie Jiang, Xiaodong Li, Qingxiu Zhong, Zhixiang Wang, Zhengshan Yi, Zhongxin Zheng, Changxin Yin, Rui Cao, Libin Liao, Fanyi Meng
Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly(+)AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly(-)AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly(+)AML and Ly(-)AML...
2015: Disease Markers
Renu Sukumaran, Rekha A Nair, Priya Mary Jacob, Kunjulekshmi Amma Raveendran Nair Anila, Shruthy Prem, Rajeswary Binitha, Parukuttyamma Kusumakumary
INTRODUCTION: Mixed phenotype acute leukemia (MPAL) is a rare subset of acute leukemia where the blasts exhibit lineage specific antigens of more than one lineage. Flow cytometric immunophenotyping is essential for the diagnosis of MPAL and the accurate diagnosis highly depends on the panel of markers used. The precise incidence of MPAL is uncertain as various institutions use different combinations of antibodies to assign the blasts to a particular lineage. AIM: The aim was to study the immunoprofile of acute leukemia including aberrant antigen expressions and to study the incidence, clinical features, laboratory findings, and immunophenotype of MPAL in our institution...
April 2015: Indian Journal of Pathology & Microbiology
Anupam Sarma, Munlima Hazarika, Debabrata Das, Avdhesh Kumar Rai, Jagannath Dev Sharma, Chidananda Bhuyan, Amal Chandra Kataki
BACKGROUND: Acute leukemia is a heterogenous disease having diverse phenotypes. Immunophenotyping by flowcytometry is essential for diagnosis of myeloid and lymphoid subtypes. Aberrant phenotype incidence is controversial and dissimilar results have been reported by different groups. OBJECTIVES: Purpose of the study was to determine the incidence of aberrant phenotypes in North East Indian patients with acute leukemia. METHODS: We analysed a total of 100 cases (AML = 36, ALL = 61, MPAL = 3) by multiparametric flow cytometry using an acute panel of monoclonal antibodies (MoAbs)...
2015: Cancer Biomarkers: Section A of Disease Markers
Hiroaki Shimizu, Takayuki Saitoh, Shinichiro Machida, Shinichi Kako, Noriko Doki, Takehiko Mori, Toru Sakura, Yoshinobu Kanda, Heiwa Kanamori, Shuichi Miyawaki, Shinichiro Okamoto
Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo-SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo-SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method...
November 2015: European Journal of Haematology
Ofir Wolach, Richard M Stone
Mixed-phenotype acute leukemia (MPAL) encompasses a heterogeneous group of rare leukemias in which assigning a single lineage of origin is not possible. A variety of different terms and classification systems have been used historically to describe this entity. MPAL is currently defined by a limited set of lineage-specific markers proposed in the 2008 World Health Organization monograph on classification of tumors of hematopoietic and lymphoid tissues. In adult patients, MPAL is characterized by relative therapeutic resistance that may be attributed in part to the high proportion of patients with adverse cytogenetic abnormalities...
April 16, 2015: Blood
Jing Lu, Neetika Ashwani, Mingying Zhang, Hailong He, Jun Lu, Yi Wang, Wenli Zhao, Lan Cao, Zhenghua Ji, Yaxiang He, Yiping Hunag, Ruihua Chen, Shaoyan Hu
Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia with a poor clinical outcome which lacks specific therapy. To evaluate the therapeutic efficiency of CCLG-2008 protocol used for acute lymphoblastic leukemia (ALL) in China on MPAL children who were initially diagnosed as ALL by morphology, we reviewed patients' database diagnosed as ALL and MPAL according to WHO classification and compared their outcomes from July 2008 to June 2012. Total newly enrolled ALL in this study were 309 cases by morphology, in which ten cases were identified as MPAL mainly by immunophenotyping: B+ myeloid (3/10), T+ myeloid (2/10), B + T (4/10), trilineage (1/10)...
March 2015: Indian Journal of Hematology & Blood Transfusion
Prabhu Manivannan, Vandana Puri, Venkatesan Somasundaram, Abhishek Purohit, Rahul Kumar Sharma, Mandeep Dabas, Renu Saxena
Objectives Myeloperoxidase (MPO) detection either by enzyme cytochemistry (cMPO) or flow cytometry (fMPO) plays a major role in acute leukaemia (AL) diagnosis as per World Health Organization (WHO) 2008 classification. Although 3% cMPO was recommended as positivity, no specific cut-off had been mentioned by WHO for fMPO. Various authors recommend different cut-offs ranging from 3 to 28% for fMPO. The aim of this study was to analyse fMPO cut-offs ranging from 3 to 10% in classifying AL and to assess whether a new cut-off could be suggested...
December 23, 2014: Hematology (Amsterdam, Netherlands)
Giuseppina Tota, Nicoletta Coccaro, Antonella Zagaria, Luisa Anelli, Paola Casieri, Angelo Cellamare, Angela Minervini, Crescenzio Francesco Minervini, Claudia Brunetti, Luciana Impera, Paola Carluccio, Cosimo Cumbo, Giorgina Specchia, Francesco Albano
BACKGROUND: Mixed phenotype acute leukemias (MPAL) include acute leukemias with blasts that express antigens of more than one lineage, with no clear evidence of myeloid or lymphoid lineage differentiation. T/myeloid (T/My) MPAL not otherwise specified (NOS) is a rare leukemia that expresses both T and myeloid antigens, accounting for less than 1% of all leukemias but 89% of T/My MPAL. From a molecular point of view, very limited data are available on T/My MPAL NOS. CASE PRESENTATION: In this report we describe a T/My MPAL NOS case with a complex rearrangement involving chromosomes 5 and 14, resulting in overexpression of the ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2) gene due to its juxtaposition to the T cell receptor delta (TRD) gene segment...
2014: BMC Cancer
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