Peripheral blood CD26 positive leukemic stem cells as a possible diagnostic and prognostic marker in chronic myeloid leukemia

Ebian, Huda F; Abdelnabi, Alshabrawy M.; Abdelazem, Abdallah S.; Khamis, Tarek; Fawzy, Hebatallah M.; Hussein, Samia

doi:10.1016/j.lrr.2022.100321

Cited by 4 publications

(8 citation statements)

References 26 publications

(40 reference statements)

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“…The median percentage of CD26-positive LSCs was 0.02 ranging from 0.001 to 1.77 and the median absolute CD26 LSC cells was 50.72 cells/μL with a range of 1.95 to 8048.2. CD26 positivity in all phases of CML was in concordance with other studies [ 11 - 14 ]. There appears to be a wide variation in the percentage of CD26-positive cells; some authors have calculated it as the percentage of CD26-positive cells out of the CD34+/CD38- stem cell population [ 8 , 11 , 12 ], whereas in our study and the study by Sharma et al, it was calculated both from the total WBC count and the CD34+/CD38- stem cells [ 13 ].…”

Section: Discussionsupporting

confidence: 92%

“…In the present study, CD26-positive LSCs showed a strong correlation with WBC count (rs = 6.0). Similar results were observed by Culen et al and Ebian et al [ 10 , 14 ]. Similar to Culen et al, we also classified WBC into two categories (≤150 x 10 3 /μL and >150 x 10 3 /μL) and found that absolute CD26 counts were more in the cases with high WBC counts (Z = -2.690).…”

Section: Discussionsupporting

confidence: 92%

“…Culen et al too didn’t find any relationship between CD26+ cells and Hasford, Sokal, and EUTOS [ 10 ]. Similar results were reported by Ebian et al, but they did observe a statistically significant difference after 12 months of TKI therapy between high and intermediate Sokal risk scores [ 14 ]. In the present study, CD26-positive LSCs showed a strong correlation with WBC count (rs = 6.0).…”

Section: Discussionsupporting

confidence: 88%

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Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia

Kana,

John,

Basu

et al. 2024

Cureus

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Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

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Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia

Kana,

John,

Basu

et al. 2024

Cureus

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“…CD34 + CD38 − CD26 + PB cells were correlated with BCR::ABL1 transcript in early CP-CML [36]. In contrast, interim analyses of the PROSPECTIVE FLOWERS study revealed that PB BCR::ABL1 + measurement was not associated with CD26 + LSC levels after initiation of TKI therapy, although CD26 + LSC levels at diagnosis could predict subsequent responses to TKIs [37].…”

Section: Cd26mentioning

confidence: 84%

The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities

Patterson

Copland

2023

Curr Hematol Malig Rep

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Purpose of Review Tyrosine kinase inhibitors (TKIs) are very successful for the treatment of chronic myeloid leukaemia (CML) but are not curative in most patients due to persistence of TKI-resistant leukaemia stem cells (LSCs). The bone marrow immune microenvironment (BME) provides protection to the LSC through multidimensional interactions, driving therapy resistance, and highlighting the need to circumvent these protective niches therapeutically. This review updates the evidence for interactions between CML cells and the immune microenvironment with a view to identifying targetable therapeutic vulnerabilities and describes what is known about the role of immune regulation in treatment-free remission (TFR). Recent Findings Intracellular signalling downstream of the chemotactic CXCL12-CXCR4 axis, responsible for disrupted homing in CML, has been elucidated in LSCs, highlighting novel therapeutic opportunities. In addition, LSCs expressing CXCL12-cleaving surface protein CD26 were highly correlated with CML burden, building on existing evidence. Newer findings implicate the adhesion molecule CD44 in TKI resistance, while JAK/STAT-mediated resistance to TKIs may occur downstream of extrinsic signalling in the BME. Exosomal BME-LSC cross-communication has also been explored. Finally, further detail on the phenotypes of natural killer (NK) cells putatively involved in maintaining successful TFR has been published, and NK-based immunotherapies are discussed. Summary Recent studies highlight and build on our understanding of the BME in CML persistence and TKI resistance, pinpointing therapeutically vulnerable interactions. Repurposing existing drugs and/or the development of novel inhibitors targeting these relationships may help to overcome these issues in TKI-resistant CML and be used as adjuvant therapy for sustained TFR.

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“… 99 CD26, perhaps as a marker of LSCs, can be used as an alternative to detect response, especially for BCR-ABL-independent CML cells; however, it is also difficult to detect small numbers of CD26-positive LSCs. 100 Thus, currently, the monitoring of CML patients revolves around the molecular response.…”

Section: Introductionmentioning

confidence: 99%

Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review

Rinaldi¹,

Winston²

2023

JBM

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Chronic myeloid leukemia (CML) is one of the most common leukemias occurring in the adult population. The course of CML is divided into three phases: the chronic phase, the acceleration phase, and the blast phase. Pathophysiology of CML revolves around Philadelphia chromosome that constitutively activate tyrosine kinase through BCR-ABL1 oncoprotein. In the era of tyrosine kinase inhibitors (TKIs), CML patients now have a similar life expectancy to people without CML, and it is now very rare for CML patients to progress to the blast phase. Only a small proportion of CML patients have resistance to TKI, caused by BCR-ABL1 point mutations. CML patients with TKI resistance should be treated with second or third generation TKI, depending on the BCR-ABL1 mutation. Recently, many studies have shown that it is possible for CML patients who achieve a long-term deep molecular response to stop TKIs treatment and maintain remission. This review aimed to provide an overview of CML, including its pathophysiology, clinical manifestations, the role of stem cells, CML treatments, and treatment-free remission.

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Peripheral blood CD26 positive leukemic stem cells as a possible diagnostic and prognostic marker in chronic myeloid leukemia

Cited by 4 publications

References 26 publications

Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia

Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia

The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities

Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review

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