High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells

Nakase, Kazunori; Kita, K; Kyo, Taiichi; Tsuji, Kota; Katayama, Naoyuki

doi:10.1016/j.canep.2012.03.011

Cited by 14 publications

(14 citation statements)

References 12 publications

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“…The serum sIL2-R levels have been reported to be significantly elevated in patients with CD25-and CD4-positive AML (16), and higher sIL-2R levels in patients with AML are associated with a poor prognosis (18). In the setting of malignant lymphoma, no distinct correlations between the CD25 expression on B-lymphoma cells and the sIL-2R level have been observed, and most CD25-expressing cells in the tumors are T-cells (19).…”

Section: Discussionmentioning

confidence: 81%

Acute Myeloid Leukemia Concurrent with Spinal Epidural Extramedullary Myeloid Sarcoma Accompanied by a High CD25 Expression and the <i>FLT3-ITD</i> Mutation

et al. 2014

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Myeloid sarcoma (MS) is an extramedullary myeloid tumor that sometimes presents with antedating systemic leukemia, leading physicians to the misdiagnosis of lymphoma. CD25 is expressed in 13% of patients with acute myeloid leukemia (AML), and its expression is associated with FLT3-ITD mutations, an elevated serum soluble interleukin 2 receptor (sIL-2R) level and a lower survival rate. However, there are no reports concerning the relationship between MS and the CD25 expression. We herein report a case of AML accompanied by thoracic epidural MS with a high CD25 expression, the FLT3-ITD mutation and an extremely elevated serum sIL-2R level in a 59-year-old man who presented with paraplegia.

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Section: Discussionmentioning

confidence: 81%

Acute Myeloid Leukemia Concurrent with Spinal Epidural Extramedullary Myeloid Sarcoma Accompanied by a High CD25 Expression and the <i>FLT3-ITD</i> Mutation

et al. 2014

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“…However, monocytic differentiation was not statistically significantly associated with either OS (P = 0.120) or EFS (P = 0.222). Nakase et al found that high serum levels of soluble interleukin-2 receptor (sIL-2R) in AML were correlated with a shorter OS and with CD4 expression on blast cells [28]. It has been suggested that sIL-2R may be involved with cell-to-cell interactions regulating growth and survival of AML cells [29].…”

Section: Discussionmentioning

confidence: 99%

Expression of CD4 is correlated with an unfavorable prognosis in wild‐type NPM1, FLT3‐ITD‐negative cytogenetically normal adult acute myeloid leukemia

Guo

Atenafu

Schimmer

et al. 2017

Int J Lab Hematology

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“…Although not unique to hematologic malignancy, increased CD25 expression can be detected via shedding of this receptor (7,8). Indeed, high soluble IL2R-a serum levels have helped identify patients with poorer prognoses in diffuse large B-cell lymphoma, cutaneous lymphomas, follicular lymphoma, AML, acute lymphoblastic leukemia, Hodgkin lymphoma (9)(10)(11)(12)(13)(14), and are used as a part of a prognostic index in ATLL (15).…”

Section: Introductionmentioning

confidence: 99%

ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Flynn

Zammarchi

Tyrer

et al. 2016

Molecular Cancer Therapeutics

109

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Despite the many advances in the treatment of hematologic malignancies over the past decade, outcomes in refractory lymphomas remain poor. One potential strategy in this patient population is the specific targeting of IL2R-α (CD25), which is overexpressed on many lymphoma and leukemic cells, using antibody-drug conjugates (ADC). ADCT-301 is an ADC composed of human IgG1 HuMax-TAC against CD25, stochastically conjugated through a dipeptide cleavable linker to a pyrrolobenzodiazepine (PBD) dimer warhead with a drug-antibody ratio (DAR) of 2.3. ADCT-301 binds human CD25 with picomolar affinity. ADCT-301 has highly potent and selective cytotoxicity against a panel of CD25-expressing human lymphoma cell lines. Once internalized, the released warhead binds in the DNA minor groove and exerts its potent cytotoxic action via the formation of DNA interstrand cross-links. A strong correlation between loss of viability and DNA cross-link formation is demonstrated. DNA damage persists, resulting in phosphorylation of histone H2AX, cell-cycle arrest in G-M, and apoptosis. Bystander killing of CD25-negative cells by ADCT-301 is also observed. In vivo, a single dose of ADCT-301 results in dose-dependent and targeted antitumor activity against both subcutaneous and disseminated CD25-positive lymphoma models. In xenografts of Karpas 299, which expressed both CD25 and CD30, marked superiority over brentuximab vedotin (Adcetris) is observed. Dose-dependent increases in DNA cross-linking, γ-H2AX, and PBD payload staining were observed in tumors in vivo indicating a role as relevant pharmacodynamic assays. Together, these data support the clinical testing of this novel ADC in patients with CD25-expressing tumors. Mol Cancer Ther; 15(11); 2709-21. ©2016 AACR.

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High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells

Cited by 14 publications

References 12 publications

Acute Myeloid Leukemia Concurrent with Spinal Epidural Extramedullary Myeloid Sarcoma Accompanied by a High CD25 Expression and the <i>FLT3-ITD</i> Mutation

Acute Myeloid Leukemia Concurrent with Spinal Epidural Extramedullary Myeloid Sarcoma Accompanied by a High CD25 Expression and the <i>FLT3-ITD</i> Mutation

Expression of CD4 is correlated with an unfavorable prognosis in wild‐type NPM1, FLT3‐ITD‐negative cytogenetically normal adult acute myeloid leukemia

ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

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