Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Motoki; Tomizawa, Daisuke; Eguchi, Mariko; Kaneko, Akiko; Ono, Ryo; Sato, Kaori; Suzuki, Naohiko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki; Ishikawa, Fumihiko

doi:10.1182/blood-2014-03-563304

Cited by 49 publications

(55 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to the previous reports that CD9 is preferentially expressed on MLLr acute lymphoblastic leukemia (ALL) cells, but not normal cells from the same patient, 20 most of the MLL-AF9 translocated cells expressed CD9 irrespective of CD34 status, in contrast to control cells, which lacked CD9 expression ( Figure 5A). CD9 expression progressively increased over time in culture comparable to PCR band intensity of MLL-AF9 and reciprocal AF9-MLL fusions (compare Figure 4C and Figure 5B), suggesting a positive correlation between CD9 expression and translocation.…”

Section: Mll-af9 Translocated Cells Display Immature Phenotypes and Psupporting

confidence: 77%

“…[34][35][36][37][38] Recently, Aoki et al described CD9 expression on the surface of MLLr ALL cells from patients, whereas normal HSPCs from the same patients did not express CD9. 20 Our studies and analysis of public databases (www.oncomine.org) showed relatively high expression of CD9 in MLLr AMLs. 21,22 Thus, although CD9 is not exclusively expressed by MLLr leukemia cells, our data suggest that it may serve as a surrogate marker for the detection and possible enrichment of genomeedited HSPCs with t(9;11) from among the much more abundant normal HSPCs in early cultures.…”

Section: Org Frommentioning

confidence: 99%

See 1 more Smart Citation

MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Mll-af9 Translocated Cells Display Immature Phenotypes and Psupporting

confidence: 77%

Section: Org Frommentioning

confidence: 99%

MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing

et al. 2018

View full text Add to dashboard Cite

show abstract

“…28 In addition, CD9, CD32, and CD24 were differentially overexpressed in MLL-r LIC compared with normal hematopoietic stem cells. By targeting these surface molecules that are selectively expressed in MLL-r LIC with recently developed immunotherapeutic modalities such as bi-specific T-cell engager (BiTE) antibodies or chimeric antigen receptor (CAR) T cells, it may be possible to treat MLL-r ALL more effectively while minimizing treatment-related hematopoietic adverse events.…”

Section: Leukemia-initiating Cells In Infant Mll-r Allmentioning

confidence: 99%

Recent progress in the treatment of infant acute lymphoblastic leukemia

Tomizawa

2015

Pediatrics International

Self Cite

View full text Add to dashboard Cite

Treatment of infants with acute lymphoblastic leukemia (ALL), especially those with mixed lineage leukemia (MLL) rearrangement (MLL-r), which account for approximately 80% of cases, is still a major challenge for pediatric hematologists and oncologists worldwide. Continuing efforts by collaborative clinical study groups in Europe, North America, and Japan have rescued approximately half of the MLL-r ALL patients with intensive chemotherapy with or without allogeneic hematopoietic stem cell transplantation. Recent progress has clarified the unique mechanism of MLL-r ALL: the aberrant methylation and histone modifications via DOT1L and other related molecules by MLL fusion proteins lead to leukemogenetic gene expression, thus to overt leukemia. In order to overcome this dismal subtype of ALL, novel targeted therapy based on leukemia biology is urgently needed. Due to the extreme rarity of the disease, collaboration between the study groups in Europe (Interfant), North America (Children's Oncology Group), and Japan (Japanese Pediatric Leukemia/Lymphoma Study Group) is under way.Key words acute lymphoblastic leukemia, epigenetics, hematopoietic stem cell transplantation, infant, mixed lineage leukemia.Acute lymphoblastic leukemia (ALL), a malignant disorder of lymphoid progenitor cells, is the most common type of malignant neoplasms in children and adolescents, with approximately 444-532 cases diagnosed annually in Japan. 1 Optimal use of "old drugs", developed between the 1950s and 1970s under successive collaborative clinical trials, has improved the outcome of childhood ALL to achieve an event-free survival (EFS) rate of 80.4-87.2% and an overall survival (OS) rate of 91.8-93.5% in recently completed clinical trials. [2][3][4][5] The progress in the treatment of infant ALL (diagnosed at age <12 months), however, is lagging behind compared with the treatment of children ≥1 year: EFS and OS remain at 41.7-50.9% and 44.8-60.5%, respectively (Table 1). 9,[11][12][13] In this review, advances in the pathobiology and clinical management of ALL in infants is described. Epidemiology and characteristicsInfant ALL accounts for <5% of childhood ALL, with 20-25 new cases diagnosed annually in Japan. In children ≥1 year, ALL comprises 75-80% of all childhood leukemia because of the high peak incidence of B-lineage ALL between the age of 2 and 5 years, with a predominance in boys. In contrast, the incidence of ALL in infants is the same as that of acute myeloid leukemia (AML), with a slight predominance in girls. 1,11 Biologically and clinically, infant ALL consists of two distinct subtypes: one involves rearrangements of mixed lineage leukemia (MLL also called KMT2A), which accounts for approximately 80% of infant ALL; and the other with germline MLL. Infant ALL with rearranged MLL (MLL-r) is a highly aggressive leukemia with high white blood cell (WBC) count and frequent involvement of extramedullary sites including the central nervous system (CNS) at diagnosis. 9,11 In addition, MLL-r ALL has a very immature CD10-ne...

show abstract

“…9, 10, 11, 12 We investigated the reason for these ambiguous results by observing the expression of these markers even at single cell level in high temporal resolution.…”

mentioning

confidence: 99%

Plastic CD34 and CD38 expression in adult B–cell precursor acute lymphoblastic leukemia explains ambiguity of leukemia-initiating stem cell populations

et al. 2016

View full text Add to dashboard Cite

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Cited by 49 publications

References 75 publications

MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing

MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing

Recent progress in the treatment of infant acute lymphoblastic leukemia

Plastic CD34 and CD38 expression in adult B–cell precursor acute lymphoblastic leukemia explains ambiguity of leukemia-initiating stem cell populations

Contact Info

Product

Resources

About