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Ph+ mixed phenotypic leukemia

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https://www.readbyqxmd.com/read/27233483/the-philadelphia-chromosome-in-leukemogenesis
#1
REVIEW
Zhi-Jie Kang, Yu-Fei Liu, Ling-Zhi Xu, Zi-Jie Long, Dan Huang, Ya Yang, Bing Liu, Jiu-Xing Feng, Yu-Jia Pan, Jin-Song Yan, Quentin Liu
The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region-proto-oncogene tyrosine-protein kinase (BCR-ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentiation, and conferring resistance to cell death...
2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27150875/two-elderly-patients-with-philadelphia-chromosome-positive-mixed-phenotype-acute-leukemia-who-were-successfully-treated-with-dasatinib-and-prednisolone
#2
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
https://www.readbyqxmd.com/read/26448695/mixed-phenotype-acute-leukemia-with-two-immunophenotypically-distinct-b-and-t-blasts-populations-double-ph-chromosome-and-complex-karyotype-report-of-an-unusual-case
#3
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
https://www.readbyqxmd.com/read/25605373/how-i-treat-mixed-phenotype-acute-leukemia
#4
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
https://www.readbyqxmd.com/read/24750307/philadelphia-chromosome-positive-mixed-phenotype-acute-leukemia-in-the-imatinib-era
#5
Hiroaki Shimizu, Akihiko Yokohama, Nahoko Hatsumi, Satoru Takada, Hiroshi Handa, Toru Sakura, Yoshihisa Nojima
Although the introduction of imatinib dramatically improved the outcomes for patients with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph + BCP-ALL), the survival benefit of imatinib has not been assessed in the context of Ph + mixed phenotype acute leukemia (Ph + MPAL). To clarify this important issue, we studied 42 Ph+ acute leukemia (Ph + AL) patients who received intensive chemotherapy and concurrent administration of imatinib. Of the 42 Ph + AL patients, 13 (31%) patients were categorized as Ph + MPAL (positive for both myeloid and B-cell lineage), 27 (64%) were categorized as Ph + BCP-ALL, and two (5%) were categorized as Ph + acute myeloid leukemia...
October 2014: European Journal of Haematology
https://www.readbyqxmd.com/read/24532437/successful-treatment-of-philadelphia-chromosome-positive-mixed-phenotype-acute-leukemia-by-appropriate-alternation-of-second-generation-tyrosine-kinase-inhibitors-according-to-bcr-abl1-mutation-status
#6
Chika Kawajiri, Hiroaki Tanaka, Shinichiro Hashimoto, Yusuke Takeda, Shio Sakai, Toshiyuki Takagi, Masahiro Takeuchi, Chikako Ohwada, Emiko Sakaida, Naomi Shimizu, Chiaki Nakaseko
Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph(+)MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph(+)MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP)...
April 2014: International Journal of Hematology
https://www.readbyqxmd.com/read/24156417/-clinical-and-laboratorial-analysis-for-15-adult-cases-of-mixed-phenotypic-acute-leukemia-with-ph-chromosome-and-or-positive-bcr-abl
#7
Ling-Zhi Yan, Su-Ning Chen, Na-Na Ping, Qin-Rong Wang, Hong Liu, Zi-Xuan Ding, Ming-Qing Zhu, Jian-Ying Liang, Dan-Dan Liu, Jian-Nong Cen, Jin-Lan Pan, Hui-Ying Qiu, Ai-Ning Sun, De-Pei Wu
The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17...
October 2013: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/23475500/mixed-phenotypic-acute-leukemia-with-two-immunophenotypically-distinct-blast-populations-report-of-an-unusual-case
#8
Khaliqur Rahman, Seena George, Apoorvi Tewari, Anurag Mehta
Mixed phenotypic acute leukemia (MPAL) is a rare disorder with an incidence of less than 2% of all acute leukemia using the recent 2008 WHO criteria. Common subtypes encountered are the B/myeloid and T/myeloid; B/T or trilineage MPAL being an exception. We discuss here a case of 20-year-male patient who presented with pallor and generalised lymphadenopathy. Peripheral blood smear examination showed presence of 61% blasts of lymphoid morphology. Immunophenotyping by multicolor flow cytometry showed two distinct populations of blasts with T and B phenotype respectively...
May 2013: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/22015493/clinical-characteristics-and-outcomes-of-mixed-phenotype-acute-leukemia-with-philadelphia-chromosome-positive-and-or-bcr-abl-positive-in-adult
#9
Ying Wang, Min Gu, Yingchang Mi, Lugui Qiu, Shougeng Bian, Jianxiang Wang
Knowledge of mixed phenotype acute leukemia (MPAL) with t(9;22)(q34;q11.2) and/or bcr-abl (Ph-positive MPAL) is limited. In this report, we review 21 adult patients with Ph-positive and/or bcr-abl positive MPAL. They were predominantly male, and presented with high WBC counts; 61.9% patients had WBC counts higher than 30 × 10(9)/L, and 33.3% patients had WBC counts higher than 100 × 10(9)/L. Electron microscopy (EM)-determined positivity for myeloperoxidase (MPO) should be considered for the classification of acute leukemia because MPO was positive by EM and flow cytometry only in 14...
December 2011: International Journal of Hematology
https://www.readbyqxmd.com/read/21933581/matrix-metalloproteinase-9-was-involved-in-the-immuno-modulatory-defect-of-mesenchymal-stem-cell-from-chronic-myeloid-leukemia-patients
#10
Xi-Shan Zhu, Wei Shi, Guang-Yu An, Hong-Mei Zhang, Yu-Guang Song, You-Bin Li
BACKGROUND: Overwhelming evidences on chronic myeloid leukemia (CML) indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. METHODS: We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property...
August 2011: Chinese Medical Journal
https://www.readbyqxmd.com/read/21378478/-acute-leukemia-of-ambiguous-lineage-with-monosomy-7-and-philadelphia-chromosome
#11
Yasufumi Kawasaki, Tatsuki Nakazora, Munehiro Suzukawa, Takayuki Tominaga, Kenji Shinohara
A 67-year-old female was admitted with a diagnosis of acute leukemia. Immature blasts did not show cytoplasmic granules and were POX(-), ES(-), and PAS(+). Flow cytometry of leukemic cells demonstrated positivity for CD7, CD10, CD19, CD13, CD34, HLA-DR, and coexpression of CD7 and CD34, CD10 and HLA-DR, and CD19 and CD13. Cytogenetic analysis demonstrated -7 and t(9;22)(q34;q11.2), and genomic studies demonstrated minor BCR/ABL chimeric mRNA and rearrangements of IgH and TCR. These findings indicated the clonal proliferation of leukemic blasts that expressed a mixed phenotype...
January 2011: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/21228332/mixed-phenotype-acute-leukemia-clinical-and-laboratory-features-and-outcome-in-100-patients-defined-according-to-the-who-2008-classification
#12
Estella Matutes, Winfried F Pickl, Mars Van't Veer, Ricardo Morilla, John Swansbury, Herbert Strobl, Andishe Attarbaschi, Georg Hopfinger, Sue Ashley, Marie Christine Bene, Anna Porwit, Alberto Orfao, Petr Lemez, Richard Schabath, Wolf-Dieter Ludwig
The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acute lymphoblastic leukemia (ALL; 43%), acute myeloid leukemia (AML; 42%), or inconclusive (15%). Immunophenotyping disclosed B + myeloid (59%), T + myeloid (35%), B + T (4%), or trilineage (2%) combinations...
March 17, 2011: Blood
https://www.readbyqxmd.com/read/21157160/-variant-philadelphia-chromosome-identified-by-interphase-fluorescence-in-situ-hybridization-fish-without-evidence-on-g-banded-karyotyping-and-metaphase-fish
#13
Mi Kyung Kim, Yeung Chul Mun, Chu Myong Seong, Wha Soon Chung, Jungwon Huh
A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46,XY,t(9;22)(q34;q11...
December 2010: Korean Journal of Laboratory Medicine
https://www.readbyqxmd.com/read/15223656/a-child-with-philadelphia-positive-ph-acute-leukemia-with-myeloid-morphology-one-case-of-stem-cell-origin
#14
Rocío Hassan, Ivone Otazú, Maria Helena Ornellas, Virginia Pires, Maria Kadma Carriço, Héctor Seuánez, Daniel Tabak, Ilana Zalcberg
Philadelphia positive (Ph+) acute myeloid leukemia (AML) is a rare and heterogeneous condition, mainly reported in adults, associated to poor prognosis and unfavorable response to therapy. Here we report clinical and laboratory findings in an 8-year-old patient diagnosed with Ph+ acute leukemia with myeloid (FAB M4) morphology. The patient consistently expressed variable levels of m-bcr, e1a2 transcripts during a 42-month follow-up after two different stem cell transplantation protocols. An immunophenotypic switch was documented, from a mixed, myeloid-lymphoid lineage to a full lymphoid phenotype following stem cell transplants, in association with an immature B-cell gene rearrangement profile and clonal instability during clinical progression...
September 2004: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/12411098/serum-free-culture-of-dendritic-cells-from-patients-with-chronic-myeloid-leukemia-in-vitro-and-estimation-of-their-cytotoxicity
#15
Wenli Zhao, Peini Xing, Xucang Wei, Tong Wang, Didi Yang, Meisheng Li
OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHODS: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4)...
September 2002: Chinese Medical Journal
https://www.readbyqxmd.com/read/11343772/additional-t-11-17-q23-q21-in-a-patient-with-philadelphia-positive-mixed-lineage-antigen-expressing-leukemia
#16
K Nishii, E Usui, M Sakakura, E Miyata, S A Ridge, A M Ford, M Masuya, F Chen, H Mitani, M Yamaguchi, N Katayama, K Kita, H Shiku
We describe very uncommon phenotypic and cytogenetic findings in a 40-year-old female with blast phase of Philadelphia chromosome (Ph)-positive CML. In addition to the t(9;22)(q34;q11) that was detected in all metaphases, a t(11;17)(q23;q21) was identified in 15 of 20 metaphases. Reverse transcription-polymerase chain reaction showed the major and minor bcr/abl fusion transcripts in the cells from a bone marrow (BM) sample. Fluorescence in situ hybridization (FISH) analysis also showed that fusion signals of the bcr and abl probes were found in 95% of blastic cells and in 64% of neutrophils...
April 1, 2001: Cancer Genetics and Cytogenetics
https://www.readbyqxmd.com/read/10936868/a-de-novo-philadelphia-chromosome-positive-acute-mixed-lineage-leukemia-with-both-major-and-minor-bcr-abl-mrna-transcripts
#17
T Tarumoto, S Imagawa, K Ohmine, A Mano, T Nagai, M Takatoku, K Muroi, K Hatake, K Ozawa
A patient with a Philadelphia chromosome (Ph)-positive acute mixed-lineage leukemia (AMLL) expressing both major and minor BCR/ABL mRNA transcripts is described. Phenotypic analysis of the leukemic blasts revealed positivity for both myeloid and B-cell lineages. Southern blot analysis showed a rearrangement of the immunoglobulin heavy chain (IgH) gene. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed the expression of both major and minor BCR/ABL mRNA transcripts. To our knowledge, this is the first report of AMLL expressing both major and minor BCR/ABL mRNA transcripts and rearrangement of the IgH gene...
September 2000: American Journal of Hematology
https://www.readbyqxmd.com/read/10348149/generation-of-dendritic-cells-from-patients-with-chronic-myelogenous-leukemia
#18
M Heinzinger, C F Waller, A von den Berg, A Rosenstiel, W Lange
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) specialized to internalize, process, and present antigen. They have the capacity to stimulate the primary immune response of resting T-cells. We generated DCs from the adherent cell fraction of peripheral blood, as well as from purified CD34+ cells from CML patients. Characterizing DCs from ten CML patients by flow cytometry, we found that these cells are highly positive for HLA-DR, CD1a, CD23, and CD80 and negative for CD14, CD15, and CD16...
April 1999: Annals of Hematology
https://www.readbyqxmd.com/read/9107085/definition-of-acute-biphenotypic-leukemia
#19
REVIEW
E Matutes, R Morilla, N Farahat, F Carbonell, J Swansbury, M Dyer, D Catovsky
BACKGROUND AND OBJECTIVE: A minority of acute leukemias have features characteristic of both the myeloid and lymphoid lineages and for this reason are designated mixed-lineage, hybrid or biphenotypic acute leukemias (BAL). There have been difficulties in establishing whether BAL represents a distinct clinico-biological entity due to a lack of objective criteria for distinguishing BAL from acute myeloid leukemias (AML) or acute lymphoblastic leukemias (ALL) with aberrant expression of a marker from another lineage...
January 1997: Haematologica
https://www.readbyqxmd.com/read/8822936/characterization-of-primitive-subpopulations-of-normal-and-leukemic-cells-present-in-the-blood-of-patients-with-newly-diagnosed-as-well-as-established-chronic-myeloid-leukemia
#20
A L Petzer, C J Eaves, P M Lansdorp, L Ponchio, M J Barnett, A C Eaves
Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals...
September 15, 1996: Blood
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