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Mixed phenotype acute leukemia

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https://www.readbyqxmd.com/read/29140408/philadelphia-chromosome-like-mixed-phenotype-acute-leukemia-demonstrating-p2ry8-crlf2-fusion-and-jak1-mutation
#1
Sarah M Choi, John K Frederiksen, Charles W Ross, Dale L Bixby, Lina Shao
Objectives: Philadelphia chromosome-like (Ph-like) genetic alterations define a subset of B lymphoblastic leukemia/lymphoma (B-ALL), which represents a separate provisional entity in the World Health Organization 2016 updated classification. However, these alterations have not been described outside the context of B-ALL. Methods: Cytogenomic array and molecular analysis identified a Ph-like signature in a mixed-phenotype acute leukemia (MPAL), B/myeloid, confirmed using conventional immunophenotypic and cytochemical analysis...
November 11, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29137234/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#2
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118508/treatment-of-unilateral-zone-i-cytomegalovirus-retinitis-in-acute-lymphoblastic-leukemia-with-oral-valganciclovir-and-intravitreal-ganciclovir
#3
Koushik Tripathy, Kanhaiya Mittal, Pradeep Venkatesh, Sameer Bakhshi, Rohan Chawla
Cytomegalovirus retinitis (CMVR) is an opportunistic infection seen in immunocompromised patients, especially suffering from acquired immune deficiency syndrome. It is uncommonly seen in hematological malignancies and in patients on immunosuppressants. The authors present a 12-year-old girl with unilateral CMVR who was on maintenance phase therapy for mixed phenotype (B/myeloid) leukemia. Serology for human immunodeficiency virus was negative. The child was successfully treated with oral valganciclovir and repeated intravitreal ganciclovir injections...
September 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/29112013/cancer-therapy-associated-lymphoproliferative-disorders-an-under-recognized-type-of-immunodeficiency-associated-lymphoproliferative-disorder
#4
Sergio Pina-Oviedo, Roberto N Miranda, L Jeffrey Medeiros
We describe the clinicopathologic features of 17 patients who had a hematologic malignancy of various types, were treated, and subsequently developed a lymphoproliferative disorder (LPD). There were 10 men and 7 women with a median age of 59 years (range, 36 to 83 y). The primary hematologic neoplasms included: 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, 3 plasma cell myeloma, 2 acute monoblastic leukemia, and 1 case each of mixed-phenotype acute leukemia, chronic myeloid leukemia, splenic marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, T-cell prolymphocytic leukemia, and peripheral T-cell lymphoma...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29089646/automated-database-guided-expert-supervised-orientation-for-immunophenotypic-diagnosis-and-classification-of-acute-leukemia
#5
L Lhermitte, E Mejstrikova, A J van der Sluijs-Gelling, G E Grigore, L Sedek, A E Bras, G Gaipa, E S da Costa, M Novakova, E Sonneveld, C Buracchi, T de Sá Bacelar, J G Te Marvelde, A Trinquand, V Asnafi, T Szczepanski, S Matarraz, A Lopez, B Vidriales, J Bulsa, O Hrusak, T Kalina, Q Lecrevisse, M M Ayuso, M Brüggemann, J Verde, P Fernandez, L Burgos, B Paiva, C E Pedreira, J J M van Dongen, A Orfao, V H J van der Velden
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL, and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29072953/mixed-phenotype-acute-leukemia-diagnostic-criteria-and-pitfalls
#6
REVIEW
Nathan J Charles, Daniel F Boyer
Mixed-phenotype acute leukemia (MPAL) is a heterogeneous category in the World Health Organization classification that comprises acute leukemias with discrete admixed populations of myeloid and lymphoid blasts ("bilineal") or with extensive coexpression of lymphoid and myeloid markers in a single blast population ("biphenotypic"). Flow cytometric findings suggestive of MPAL are often met with consternation by pathologists and oncologists alike, owing to unfamiliarity with the disease and uncertainty about how MPAL fits into established paradigms for treatment of acute leukemia...
November 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29021517/a-rare-case-of-mixed-phenotype-acute-leukemia-b-t-cell-type
#7
Jain Monica, Mittal Dipali, Shukla Pragya, Jena Nihar
No abstract text is available yet for this article.
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28971902/mixed-phenotype-acute-leukemia-outcomes-with-allogeneic-stem-cell-transplantation-a-retrospective-study-from-the-acute-leukemia-working-party-of-the-ebmt
#8
Reinhold Munker, Myriam Labopin, Jordi Esteve, Christoph Schmid, Mohamad Mohty, Arnon Nagler
Mixed phenotype acute leukemias are infrequent and considered high-risk. The optimal treatment approach and the role of allogeneic hematopoietic stem cell transplantation are not entirely clear. In this study, we investigated 519 patients with mixed phenotype acute leukemia in first complete remission who underwent allogeneic hematopoietic stem cell transplantation between 2000 and 2014 and were reported to the Acute Leukemia Working Party of the EBMT. The median age was 38.1 years (range 18- 75), by cytogenetics, 49...
September 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28943635/ng2-antigen-is-involved-in-leukemia-invasiveness-and-central-nervous-system-infiltration-in-mll-rearranged-infant-b-all
#9
C Prieto, B López-Millán, H Roca-Ho, R W Stam, D Romero-Moya, F J Rodríguez-Baena, A Sanjuan-Pla, V Ayllón, M Ramírez, M Bardini, P De Lorenzo, M G Valsecchi, M Stanulla, M Iglesias, P Ballerini, Á M Carcaboso, J Mora, F Locatelli, A Bertaina, L Padilla, J Carlos Rodríguez-Manzaneque, C Bueno, P Menéndez
Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive...
September 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28902076/therapy-related-acute-leukemia-with-mixed-phenotype-and-novel-t-1-6-q25-p23-after-treatment-for-high-risk-neuroblastoma
#10
Sarah B Whittle, Jyotinder N Punia, Dolores López-Terrada, Amos Gaikwad, Oliver A Hampton, Andras Heczey
Neuroblastoma is the most common extracranial malignancy of childhood. Patients with high-risk disease receive multimodal treatment including chemotherapy combinations containing alkylating agents and topoisomerase inhibitors with potential for inducing therapy-related malignancy later in life. Most commonly, cytogenetic changes of pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia involve chromosome 5 or 7. Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia 30 months after treatment for high-risk neuroblastoma with biphenotypic cell surface markers and a not yet described translocation t(1;6)(q25;p23)...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28882084/genomic-characterization-of-chromosome-translocations-in-patients-with-t-myeloid-mixed-phenotype-acute-leukemia
#11
Aparna Pallavajjala, Daehwan Kim, Tongbin Li, Gabriel Ghiaur, Richard J Jones, Kathleen H Burns, Steven L Salzberg, Yi Ning
Mixed-phenotype acute leukemia (MPAL) is a progenitor type of leukemia with ambiguous expression of lineage markers. The diagnosis of MPAL is based on flow cytometric analysis of immunophenotype, which commonly identifies myeloid lineage markers as well as B- or T- lymphoid lineage markers on leukemic blasts. Due to the rare occurrence of this disease, few studies have delineated the molecular bases of MPAL. Combining conventional karyotyping with whole genomic sequencing (WGS) and RNA sequencing (RNA-seq), we report here our identification and characterization of chromosome translocations, gene mutations and gene expression profile in four patients with T/Myeloid MPAL, including two t(6;14)(q25;q32) one t(8;14)(q24...
September 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28768245/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#12
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694182/allogeneic-hematopoietic-stem-cell-transplantation-with-myeloablative-conditioning-is-associated-with-favorable-outcomes-in-mixed-phenotype-acute-leukemia
#13
Bartlomiej M Getta, Mikhail Roshal, Junting Zheng, Jae H Park, Eytan M Stein, Ross Levine, Esperanza B Papadopoulos, Ann A Jakubowski, Nancy A Kernan, Peter Steinherz, Richard J O'Reilly, Miguel-Angel Perales, Sergio A Giralt, Martin S Tallman, Brian C Shaffer
Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pretransplantation therapy, and transplantation outcomes for 36 well-characterized pediatric and adult patients with MPAL, defined according to the 2016 World Health Organization leukemia update. A predominance of acute lymphoid leukemia (ALL)-associated mutations and cytogenetic abnormalities was noted...
November 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28670077/mixed-phenotypic-acute-leukemia-with-leukemia-cutis-and-neuroleukemiosis
#14
Rona Joseph Poikayil, Geetha Narayanan, Harish Sugathan, Lali V Soman
Leukemia cutis and neuroleukemiosis are two rare extramedullary manifestations of acute leukemia. We report a 32-year-old woman with multiple skin lesions and painful peripheral neuropathy. Bone marrow biopsy and skin biopsy confirmed the diagnosis of mixed phenotypic acute leukemia. After induction chemotherapy, she attained marrow remission, her skin lesion resolved completely, and her neurologic symptoms significantly improved.
July 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28625325/importance-of-cd117-in-the-assignation-of-a-myeloid-lineage-in-acute-leukemias
#15
Alan Pomerantz, Sergio Rodríguez-Rodríguez, Roberta Demichelis-Gómez, Georgina Barrera-Lumbreras, Olga V Barrales-Benítez, María José Díaz-Huízar, Monica Goldberg-Murow, Xavier López-Karpovitch, Álvaro Aguayo
The correct classification of acute leukemias (AL) is an essential part in the evaluation of any patient with this disease. Historically, CD117 has been an important asset in the diagnosis of patients with mixed-phenotype acute leukemia (MPAL). In an attempt to simplify the diagnosis of MPAL with fewer and more lineage specific markers, the World Health Organization (WHO) proposed in 2008 a new criteria for the diagnosis of this type of AL, which excluded CD117 from the myeloid markers that are utilized to diagnose MPAL...
February 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28551327/t-cell-transcription-factor-gata-3-is-an-immunophenotypic-marker-of-acute-leukemias-with-t-cell-differentiation
#16
David M Dorfman, Elizabeth A Morgan, Ashley Pelton, Christine Unitt
T-cell transcription factor GATA-3, known to play a role in early T-cell development and in the development of T-cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T-lymphoblastic leukemia/lymphoma (22/22 cases), early T-cell precursor lymphoblastic leukemia (11/11 cases), and mixed-phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B-lymphoblastic leukemia (0/16 cases)...
July 2017: Human Pathology
https://www.readbyqxmd.com/read/28540857/an-unusual-case-of-acute-leukemia
#17
Carole Fleury, Marie Passet, Catherine Settegrana, Laurence Simon, Elise Chapiro, Amélie Trinquand, Ines Safra Zaghouani, Madalina Uzunov, Magali Le Garff-Tavernier, Marine Armand, Myrto Costopoulos
We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation...
June 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28494052/association-of-minimal-residual-disease-with-clinical-outcome-in-pediatric-and-adult-acute-lymphoblastic-leukemia-a-meta-analysis
#18
Donald A Berry, Shouhao Zhou, Howard Higley, Lata Mukundan, Shuangshuang Fu, Gregory H Reaman, Brent L Wood, Gary J Kelloff, J Milburn Jessup, Jerald P Radich
Importance: Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development. Objective: To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases...
July 13, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28459703/novel-cytogenetic-findings-in-a-case-of-mixed-phenotype-acute-leukemia-within-the-context-of-a-complex-karyotype
#19
David Shabsovich, Gary Schiller, Yalda Naeini, Robert Collins, Carlos A Tirado
BACKGROUND: Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy characterized by combinatorial aberrations involving cells of the myeloid, T-, and/or B- lineages, most often diagnosed by means of immunophenotyping in order to assess lineage-specific markers, which can still yield inconclusive diagnoses. MPAL with a complex karyotype (three or more chromosomal abnormalities) is a cytogenetic subtype of MPAL associated with a poor prognosis, but limited data is available about the cytogenetic abnormalities present in this context...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28453885/lineage-switch-under-blinatumomab-treatment-of-relapsed-common-acute-lymphoblastic-leukemia-without-mll-rearrangement
#20
Annabelle Zoghbi, Udo Zur Stadt, Beate Winkler, Ingo Müller, Gabriele Escherich
Blinatumomab is a bispecific T-cell engaging αCD19 antibody used in refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL). Recently, lineage switch to a myeloid phenotype has been described following CD19 targeting treatment in three pediatric patients with mixed lineage leukemia (MLL) rearranged ALL. We report the case of a female who received blinatumomab for a first relapse of ALL without MLL alterations. She suffered from a second relapse early after hematopoietic stem cell transplantation and was treated with blinatumomab again...
November 2017: Pediatric Blood & Cancer
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