BACKGROUND: Acute leukemia (AL), not clearly assigned to myeloid, B-lymphoid, or T-lymphoid lineage, is classified as either biphenotypic acute leukemia (BAL) based on the European Group for Immunological Classification of Leukemias (EGIL) or acute leukemia of ambiguous lineage (ALAL) encompassing acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemia (MPAL) based on the World Health Organization (WHO) criteria. METHODS: Medical records of children newly diagnosed with BAL or ALAL, based on the EGIL or the 2008/2016 WHO criteria, respectively, admitted at Chonnam National University Hospital in 2001–2017 were retrospectively reviewed. RESULTS: Twelve (3.2%) of 377 AL patients satisfied the BAL or ALAL definitions based on the EGIL or the WHO criteria, respectively. Among 12 patients including 11 with BAL and another with undefined case based on the EGIL criteria, 7 (1.9%) had ALAL based on more stringent 2016 WHO criteria (AUL, 2; MPAL, 5). One patient had MPAL with t(9;22)(q34;q11.2), BCR-ABL+, and two had MLL gene abnormality. ALL-directed regimen was associated with better complete remission rate compared with AML-directed regimen (100.0% vs. 16.7%; P=0.015). The 5-year overall survival (OS) and event-free survival (EFS) were 51.1±15.8% and 51.9±15.7%, respectively. AUL was associated with poor OS and EFS compared with MPAL (0.0% vs. 75.0±21.7%; P=0.008). CONCLUSION: Due to the rarity of the cases, future multicenter, prospective studies incorporating large number of cases are urgently warranted to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.
Child ; Classification ; Disease-Free Survival ; Humans ; Immunophenotyping ; Jeollanam-do ; Leukemia ; Leukemia, Biphenotypic, Acute ; Medical Records ; Prognosis ; Prospective Studies ; Retrospective Studies ; World Health Organization

In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia.
Adult ; Biopsy ; Biopsy, Large-Core Needle ; Bone Marrow ; Breast* ; Chromatin ; Diagnosis, Differential ; Drug Therapy ; Fatigue ; Female ; Humans ; Karyotyping ; Leukemia ; Leukemia, Biphenotypic, Acute* ; Leukemic Infiltration ; Nipples ; Peripheral Blood Stem Cell Transplantation ; Recurrence* ; Tissue Donors

No abstract available.
Aged, 80 and over ; Antimetabolites, Antineoplastic/*therapeutic use ; Azacitidine/*analogs & derivatives/therapeutic use ; Biomarkers, Tumor/analysis/genetics ; Biopsy ; Bone Marrow Examination ; Cell Lineage ; Female ; Humans ; Leukemia, Biphenotypic, Acute/*drug therapy/genetics/pathology ; Phenotype ; Remission Induction ; Treatment Outcome

Humans ; Leukemia, Biphenotypic, Acute ; Leukocytosis

OBJECTIVETo highlight the current understanding of mixed phenotype acute leukemia (MPAL).

DATA SOURCESWe collected the relevant articles in PubMed (from 1985 to present), using the terms "mixed phenotype acute leukemia", "hybrid acute leukemia", "biphenotypic acute leukemia", and "mixed lineage leukemia". We also collected the relevant studies in WanFang Data base (from 2000 to present), using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".

STUDY SELECTIONWe included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version, with no limitation of research design. The duplicated articles are excluded.

RESULTSMPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously. The clinical manifestations of MPAL are similar to other acute leukemias. The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 criteria are most widely used. MPAL does not have a standard therapy regimen. Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features, and also the experience of individual physician. The lack of effective treatment contributes to an undesirable prognosis.

CONCLUSIONOur understanding about MPAL is still limited. The diagnostic criteria have not been unified. The treatment of MPAL remains to be investigated. The prognostic factor is largely unclear yet. A better diagnostic criteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

This study was aimed to explore the expression of CD34 in patients with biphenotypic acute leukemia (BAL) and its relation with the prognosis of BAL. The flow cytometry was used to detect leukemia-associated antigen. The used monoclonal antibodys (McAb) included CD10, CD19 and CD34 for B lymphocyte lineage, CD2, CD3 and CD5 for T lymohocyte lineage, MPO, CD13 and CD33 for myeloid lineage. The finally results were respectively analyzed. The results indicated that 9 out of 216 cases of leukemia was diagnosed as BAL (4.2%). Among 9 cases of BAL, 6 cases showed the common expression of myeloid and T lymohocyte lineages (66.7%), 3 cases showed the common expression of myeloid and B lymohocyte lineages (33.3%). 4 cases of BAL displayed CD34 positive expression (44.4%). As compared with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), the BAL patients showed higher CD34 positive expression (P < 0.05). It is concluded that the BAL patients show a poor prognosis, as compared with AML or ALL patients. The therapeutic effect of BAL may negatively correlate with the CD34 positive expression.
Aged ; Antigens, CD34 ; metabolism ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Biphenotypic, Acute ; diagnosis ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

Adult ; Biopsy ; CD3 Complex ; metabolism ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Humans ; Leukemia, Biphenotypic, Acute ; metabolism ; pathology ; Lymph Nodes ; metabolism ; pathology ; Neck ; PAX5 Transcription Factor ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.
Animals ; Disease Models, Animal ; Leukemia, Biphenotypic, Acute ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion ; genetics ; Retroviridae ; genetics ; Transfection

No abstract available.
Leukemia, Biphenotypic, Acute ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Paraproteinemias ; Thrombocythemia, Essential

Acute Disease ; Antigens, CD ; analysis ; Biomarkers, Tumor ; analysis ; Chromosome Aberrations ; Diagnosis, Differential ; Humans ; Immunophenotyping ; Leukemia ; classification ; diagnosis ; genetics ; immunology ; Leukemia, Biphenotypic, Acute ; classification ; diagnosis ; genetics ; immunology ; Phenotype