Characterization of hemopoietic precursor cells in juvenile-type chronic myelocytic leukemia

Suda, Toshio; Miura, Yasusada; Mizoguchi, Hideaki; Ijima, Hiroko; Eguchi, Mitsuoki; Kaku, Hidehumi; Idé, Chizuka

doi:10.1016/0145-2126(82)90042-x

Cited by 21 publications

(5 citation statements)

References 12 publications

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“…10 Spontaneous growth of colony-forming units-granulocyte/macrophage (CFU-GM) in the absence of exogenous growth factors was also assessed according to published methods. 17, 18 Clinical and laboratory characteristics of JMML patients are shown in Table 1. All control samples were BM cells (26 fresh and 21 frozen) collected from the following subjects: healthy sibling donors of patients given BM transplantation, non-leukemic children presenting with suspected symptoms of leukemia, such as bleeding diathesis or arthralgia (Supplementary Table SI).…”

Section: Methodsmentioning

confidence: 99%

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Hasegawa

Bugarin

Giordan

et al. 2013

Blood Cancer Journal

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To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59–100%) and a specificity of 87% (CI 70–96%). Positive and negative predictive values were 71% (CI 42–92%) and 96% (CI 82–100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.

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Section: Methodsmentioning

confidence: 99%

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Hasegawa

Bugarin

Giordan

et al. 2013

Blood Cancer Journal

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“…The experiments uncovered a characteristic capacity of JMML progenitor cells for excessive formation of monocyte-macrophage colonies in vitro [23]. This feature was repeatedly observed in the context of different studies [24][25][26][27]. Cultures in semisolid media were also instrumental in elucidating the hypersensitive response of JMML progenitor cells to several hematopoietic cytokines, specifically the granulocyte-macrophage colony-stimulating factor (GM-CSF) [28,29], tumor necrosis factor α [30], and interleukin-1 [31].…”

Section: Previous Strategies Of Modeling Jmml 21 In Vitro Approachesmentioning

confidence: 74%

Induced Pluripotent Stem Cells to Model Juvenile Myelomonocytic Leukemia: New Perspectives for Preclinical Research

Wehbe

Ghanjati

Flotho

2021

Cells

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Juvenile myelomonocytic leukemia (JMML) is a malignant myeloproliferative disorder arising in infants and young children. The origin of this neoplasm is attributed to an early deregulation of the Ras signaling pathway in multipotent hematopoietic stem/progenitor cells. Since JMML is notoriously refractory to conventional cytostatic therapy, allogeneic hematopoietic stem cell transplantation remains the mainstay of curative therapy for most cases. However, alternative therapeutic approaches with small epigenetic molecules have recently entered the stage and show surprising efficacy at least in specific subsets of patients. Hence, the establishment of preclinical models to test novel agents is a priority. Induced pluripotent stem cells (IPSCs) offer an opportunity to imitate JMML ex vivo, after attempts to generate immortalized cell lines from primary JMML material have largely failed in the past. Several research groups have previously generated patient-derived JMML IPSCs and successfully differentiated these into myeloid cells with extensive phenotypic similarities to primary JMML cells. With infinite self-renewal and the capability to differentiate into multiple cell types, JMML IPSCs are a promising resource to advance the development of treatment modalities targeting specific vulnerabilities. This review discusses current reprogramming techniques for JMML stem/progenitor cells, related clinical applications, and the challenges involved.

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“…In the absence of Philadelphia chromosome and, sometimes, normal LAPA score, the diagnosis of JCML can be difficult. The in vitro excessive proliferation of monocytes or monocyte-granulocyte colonies in the absence of, or with exogenous, GM-CSF is pathognomonic for this disorder [5,6,16,17]. The third PB GM-CFE study was done at age 13 months, while the patient was still on alpha-2-IFN, and presumably reflects the in vivo effect of the drug on the in vitro growth pattern of the patient's GM-CFE.…”

Section: Discussionmentioning

confidence: 99%

Congenital juvenile chronic myelogenous leukemia: Therapeutic trial with interferon alpha‐2

Hazani

Barak

Berant

et al. 1993

Med. Pediatr. Oncol.

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A newborn with congenital juvenile chronic myelogenous leukemia (JCML) is described. The diagnosis was suggested by the characteristic clinical and hematologic presentation, and was confirmed by the results of in-vitro cultures of the hematopoietic progenitors, which showed excessive proliferation of monocytic colonies, with and without the addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF). Based on published in-vitro response of JCML cells to alpha interferon-2 (alpha IFN 2), we treated this child for 17 weeks with subcutaneous alpha interferon, 1,000,000 units per day. In contrast to previous in vitro results, treatment of this patient affected neither the clinical course of the disease, nor the in vitro growth of the peripheral blood-derived monocytic colonies.

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Characterization of hemopoietic precursor cells in juvenile-type chronic myelocytic leukemia

Cited by 21 publications

References 12 publications

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Induced Pluripotent Stem Cells to Model Juvenile Myelomonocytic Leukemia: New Perspectives for Preclinical Research

Congenital juvenile chronic myelogenous leukemia: Therapeutic trial with interferon alpha‐2

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