Aggressive nk cell leukemia lymphoma aggressive nk cell leukemia lymphoma is a catastrophic disease. Aggressive nkcell leukemia, also known as aggressive nkcell leukemialymphoma 905 is a very rare disorder in western countries, most reports coming from japan. Extranodal natural killer nk t cell lymphoma is an aggressive malignancy of putative nk cell origin, with a minority deriving from the t cell lineage. Nine of 16 cases reached diseasefree survival along followup 668 months, and a. Oct 10, 2018 aggressive nk cell leukemia ankl is a rare malignant lymphoproliferative disorder of mature nk cells closely associated with epsteinbarr virus ebv and more common in east asia than in other areas. Here we studied the possibility to induce nk cell adcc. Antibodydependent cellular cytotoxicity adcc is a major mechanism by which antitumor antibodies mediate therapeutic efficacy. Molecular basis of targeted therapy in tnkcell lymphoma. Ankl has a distinct geographic distribution with the most prevalence in asians, more commonly affecting young to middle aged adults, and is almost. Aggressive natural killer cell leukemia ankl or aggressive nkcell leukemia is a very rare and highlyaggressive cancer that is mostly observed in adults. Diagnosis and management of natural killercell malignancies. Cd19 car nk cell therapy clinical trial shows encouraging.
Natural killer nk cells play an important role in surveillance and elimination of malignant cells. We reported a typical case with presentation, immunology and cytogenetic results. Aggressive nk cell leukemia ankl is a rare malignant lymphoproliferative disease of mature nk cell type. For more than a decade, however, an impaired nk cell cytotoxic. Nk cells are found circulating throughout the body, where their frequency among lymphocytes in mice varies in different organs, ranging from approximately 1% in lymph nodes lns, 2% in the spleen, 5% in the liver, to 10% in the lung, with the largest. Rezvani led the development of md andersons car nk platform with the support of the adoptive cell therapy act platform, chronic lymphocytic leukemia moon shot and bcell lymphoma moon shot. Aggressive nkcell leukemia ankl is a rare form of nk cell neoplasm sporadically affecting people from asia and central and south america. Nk cells are best known for killing virally infected cells, and detecting and controlling. Their spontaneous cytotoxicity was first demonstrated in vitro against leukemia cell lines, and nk cells might play a crucial role in the therapy of leukemia. It often presents with a rapidly declining clinical course and a poor prognosis with a median survival of a few months. Cd56negative aggressive nk cell leukemia relapsing as. Genetically engineered car nk cells display selective. The two forms of nk cell malignancy, aggressive nk cell leukemia ankl and extranodal nk cell lymphoma of nasal type enkl are both characterized by the proliferation of tumor cells with an nk. Nk cell genotype and phenotype at diagnosis of acute.
The neoplastic natural killer nk cells usually harbor the epsteinbarr virus ebv with a latent viral infection pattern type ii. Treatment of a child with myeloidnk cell precursor acute leukemia with lasparaginase and unrelated cord blood transplantation. Dec 21, 2017 aggressive nk cell leukemia ankl is a rare form of nk cell neoplasm sporadically affecting people from asia and central and south america. Significant variations exist in the morphology of ankl tumor cells, from typical large granular lymphocyte morphology to highly atypical features with basophilic cytoplasm containing azurophilc. In addition, it has been noted a dismal prognosis in. Natural killer cells for therapy of leukemia transfus med hemother 2016. Functional characterization of nk cells in mexican. Pdf aggressive nk cell leukemia ankl is a rare malignant lymphoproliferative disorder of mature nk cells closely associated with epsteinbarr virus. The promise of natural killer nk cells as effectors in cancer cellular therapy is limited by their expression of dominant inhibitory receptors for human leukocyte antigen hla class i. Not all natural killer nk cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. Nk cell transplants have emerged as a potentially powerful approach to treating acute myeloid leukemia. Aggressive nk cell leukemia also called aggressive nk cell lymphoma, or ankl, is a very rare type of nhl. The median overall survival os is less than 2 months.
Pdf treatment of a child with myeloidnk cell precursor. Aggressive nk cell leukaemia affects younger patients, who present with poor. Functional characterization of nk cells in mexican pediatric. How i treat nktcell lymphomas blood american society of. Cord blood natural killer nk cells in leukemialymphoma. Natural killer cells, part of the innate immune system, play a role in immune responses against exogenous pathogens as well as cancer. Nk cells provide immune edge when stopping imatinib. Natural killer nk cells are a population of innate lymphoid cells exhibiting potent cytotoxic activity and cytokine production. Aggressive nkcell leukemia also called aggressive nkcell lymphoma, or ankl, is a very rare type of nhl. Geoffrey strutton, in weedons skin pathology third edition, 2010. Precursor nk cell lymphoblastic leukemialymphomareport. According to the currently applied innate lymphoid cell nomenclature, nk cells are a prototypical member of the group 1 innate lymphoid cells insofar as they produce interferon. Nk cells are found circulating throughout the body, where their frequency among lymphocytes in mice varies in different organs, ranging from approximately 1% in lymph nodes lns, 2% in the spleen, 5% in the liver, to 10% in the lung, with the largest absolute. Mar 28, 2009 myeloidnk cell leukemia is distinct entity, being different from the myeloidnk cell precursor acute leukemia and blastic nk cell lymphomaleukemia in morphology and immunotypes.
Here, we discuss how chimeric antigen receptors cars engineered to override inhibitory signaling might boost nk cell antitumor responses, independently of blockade of nk cell. Sep 20, 20 haploidentical nk cell infusion in acute myeloid leukemia nk the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The patient went to see a doctor with leucocytosis, anemia and thrombocytopenia. Recent studies have identified the existence of memorylike characteristics in some natural killer cells, and romee et al. Mar 14, 2014 precursor natural killer nk cell lymphoblastic leukemialymphoma is a rare entity defined clearly by who 2008 who classification. Aggressive nk cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. The two forms of nkcell malignancy, aggressive nkcell leukemia ankl and extranodal nkcell lymphoma of nasal type enkl are both characterized. In this issue of clinical cancer research, curti and colleagues report their experience in infusing natural killer nk cells from haploidentical kirhla class i mismatched donors in elderly acute myeloid leukemia aml patients after first complete remission cr.
The disease is usually resistant to cytotoxic agents, and no treatment has emerged as the standard of care for these patients. Extranodal natural killer nktcell lymphoma is an aggressive malignancy of putative nkcell origin, with a minority deriving from the tcell lineage. Haploidentical nkcell infusion in acute myeloid leukemia. Absolute nk cell counts were also higher among the patients, and a similar trend was observed in absolute nk cell counts 0. The development into memorylike longlived nk cells with adaptive immune properties was indicated. Inhibitionresistant cars for nk cell cancer immunotherapy.
Pathologically, the malignancy occurs in two forms, extranodal nktcell lymphoma, nasal type. We correlated nk cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia all with minimal residual disease mrd after induction chemotherapy. Case a 17yearold mexican female initially presented to an outside hospital 6 months prior with high fever, cough, and pulmonary in. Here, we present a case with nasal and bone marrow involvement, provide a. Acute lymphoblastic leukemia all is the most common cancer in children around the globe. They may be a little different from lab to lab and for children and teens.
Exploitation of natural killer cells for the treatment of. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. T and nk cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. Aggressive natural killer leukemia ankl is a rare neoplastic proliferation of mature natural killer nk cells described in the world health organization 2008, with fewer than 200 cases reported in the literature. The article by curti and colleagues highlights the potential of natural killer nk cellbased adoptive cellular immunotherapy in oncology, currently boosted by advances in the knowledge on nk cell biology and in their ex vivo gmp manipulation. Mexico city has one of the highest incidence rates of childhood leukemia worldwide with 49. Haploidentical nkcell infusion in acute myeloid leukemia nk the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Large granular lymphocytic leukemia may involve either tcells or nk cells. T and nkcell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase.
Nk cell leukemia pdf aggressive nk cell leukaemia, are generally rare, but they are more common in. We strongly recommend that you talk with a trusted. Aggressive nkcell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. Mar 26, 2012 nk cells contribute to antileukemic immune responses both by exerting direct cytotoxic activity and activating other immune cells. Understanding leukemia i page 7 normal blood cell count fast facts the ranges of blood cell counts below are for adults. Myeloidnk cell leukemia is distinct entity, being different from the myeloidnk cell precursor acute leukemia and blastic nk cell lymphomaleukemia in morphology and immunotypes. There is no gender preference, with the median age of presentation being in the third decade. Nk cells mediate a crucial graftversus leukemia effect in haploidenticalhsct to cure highrisk acute leukemia franco locatelli,1,2 daniela pende,3 michela falco,4 mariella della chiesa,5,6 alessandro moretta,5,6,y and lorenzo moretta7, natural killer nk cells are involved in innate defenses against viruses and tumors. Lymphoma occur most commonly 80% in the nose and upper aerodigestive tract, less commonly 20% in nonnasal. Cord blood natural killer nk cells in leukemialymphoma the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Oncolytic viral therapies have also shown promise in the treatment of a variety of solid cancers, leading to the recent. The four major types of leukemia are chronic lymphocytic leukemia cll, acute lymphoblastic leukemia all, chronic myeloid leukemia cml, and acute myeloid leukemia aml.
Jun 20, 20 the world health organization who classification distinguishes between 2 histopathological subtypes of nk cell malignancies. However, the pathobiology of this subset of neoplasms is not clearly defined. Cytokineinduced memorylike natural killer cells exhibit. Precursor natural killer nk cell lymphoblastic leukemialymphoma is a rare entity defined clearly by who 2008 who classification. Natural killer cellbased immunotherapy in acute myeloid. Pathologically, the malignancy occurs in two forms, extranodal nk t cell lymphoma, nasal type. Symptoms may include bleeding and bruising, feeling tired, fever, and an increased risk of infections.
The world health organization who classification distinguishes between 2 histopathological subtypes of nkcell malignancies. Aggressive natural killer cell leukemialymphoma ankl is a rare and highly aggressive nk cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with nkt cell lymphoma nktl, which has a very different prognosis. Natural killer cells british society for immunology. Leukemia, also spelled leukaemia, is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. Aggressive nk cell leukemia genetic and rare diseases. Treatment of a child with myeloid nk cell precursor acute leukemia with lasparaginase and unrelated cord blood transplantation. Virus fuels nk cell killing of leukemia blood american. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative t cell and 2 nk cell lymphoma leukemia cell lines for predictive markers of response to targeted therapy. Ankl develops most often in people from asia, central america and south america.
Listing a study does not mean it has been evaluated by the u. The most common sites of involvement are peripheral blood, bone marrow, liver and spleen. Natural killer cell immune escape in acute myeloid leukemia. Jun 17, 2017 aggressive natural killer cell leukemia lymphoma ankl is a rare and highly aggressive nk cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with nk t cell lymphoma nktl, which has a very different prognosis. Apr 28, 2018 aggressive natural killer cell leukemia ankl or aggressive nk cell leukemia is a very rare and highlyaggressive cancer that is mostly observed in adults. How i treat nktcell lymphomas blood american society. Aggressive nk cell leukemia, also known as aggressive nk cell leukemia lymphoma 905 is a very rare disorder in western countries, most reports coming from japan. Aggressive nkcell leukemia canadian cancer society. The differential diagnoses of this mature nk cell neoplasm included ankl and systemic involvement by enkl. The body makes large numbers of nk cells that are larger than normal.
Precursor nk cell lymphoblastic leukemialymphomareport of a. Cancers free fulltext induction of nk cell reactivity. Aggressive nk cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells nk cells and a rapidly declining clinical course. We describe a patient with an aggressive nkcell leukemia with a rare cold agglutinin antibody. Ankl is closely associated with epsteinbarr virus ebv 7, 8, with only 10% of ankl. Nk cells contribute to antileukemic immune responses both by exerting direct cytotoxic activity and activating other immune cells. Cold agglutinin induced autoimmune hemolytic anemia and.
Aggressive nkcell leukemialymphoma aggressive nkcell leukemialymphoma is a catastrophic disease. Leukemia is called lymphocytic or lymphoblastic if the cancerous change takes place in a type of marrow cell that forms lymphocytes a type of white blood cell. Pdf long term survival in aggressive nkcell leukemia. Aggressive natural killer cell leukemia ankl is extremely rare and habitually manifests as a systemic disease with multiorgan failure that rapidly evolves to death. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative tcell and 2 nkcell lymphomaleukemia cell lines for predictive markers of response to targeted.
These blood cells are not fully developed and are called blasts or leukemia cells. At present, we evaluate an fcoptimized amino acid substitutions s239di332e flt3 antibody termed 4g8sdiem flysyn in patients with acute myeloid leukemia nct02789254. In addition, it has been noted a dismal prognosis in mexican and hispanic all. Leukemia of natural killer nk cells was first described in 19861, 2. Aggressive nk cell leukemia an overview sciencedirect. Following preliminary diagnosis of an nk cell lymphoma leukemia, extensive imaging studies including ct scans of the neck, chest, abdomen and pelvis with and without contrast, ct scan of the brain without contrast and petct scan of the head and neck were performed to identify any lesions. Ankl is prevalent among eastern asian populations compared with western countries and develops mainly in the relatively young 46. Natural killer nk cells are lymphocytes in the same family as t and b cells, coming from a common progenitor.