Downregulation of Lymphoid enhancer‐binding factor 1 (<i>LEF‐1)</i> expression (by immunohistochemistry and/ flow cytometry) in chronic Lymphocytic Leukemia with atypical immunophenotypic and cytologic features

Soliman, Dina Sameh; Kuwari, Einas Al; Siveen, Kodappully Sivaraman; Al-Abdulla, Rajaa; Chandra, Prem; Yassin, Mohamed A; Nashwan, Abdulqadir J.; Hilmi, Feryal A; Taha, Ruba; Nawaz, Zafar; El-Omri, Halima; Mateo, Jericha M.; Al‐Sabbagh, Ahmad

doi:10.1111/ijlh.13420

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…According to the IHC results, LEF-1 was positive in all the CLL/SLL cases in the current study, which was similar to some previous studies (14). Moreover, the sensitivity and specificity for LEF-1 were 100%, which were higher than reported in literature (6).…”

Section: Resultscontrasting

confidence: 63%

A Comparison of Bone Marrow Flow Cytometry Findings and Bone Marrow Biopsy İmmunohistochemical Findings in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Methodological Study

Özdemir

Yavaşoğlu

Şenol

et al. 2023

esmj

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Introduction: The diagnosis of chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), which also includes atypical forms, can be very difficult. The aim of this study is to compare immunohistochemical (IHC) and flow cytometric (FC) immunophenotyping methods in the CLL/SLL, the most common mature B-cell leukemia/lymphoma of adults, in bone marrow biopsy. In these two methods, it is to determine the minimum panels that can differentiate CLL/SLL from other mature B-cell leukemia/lymphomas. Material and Method: The study included 68 adult patients diagnosed with mature B cell leukemia/lymphoma. Final diagnoses were made on the basis of peripheral smear, bone marrow aspirate, bone marrow biopsy, IHC and FC analysis, clinical and genetic studies. Cell counts, final diagnosis and immunophenotyping were compared with both methods. Cytogenic findings were evaluated. The sensitivity, specificity, positive and negative predictive values of IHC and FC results for CLL/SLL were calculated. Results: CLL/SLL was diagnosed in 64.7% of the cases and non- CLL/SLL in 35.29% of the cases. The median age was 66.50 years, 69.18% male and 30.82% female. The diagnosis compatibility in FC and IHC was found to be highest in hairy cell leukemia/lymphoma with 100%, and in CLL/SLL with 90%. In other lymphomas, a definitive diagnosis could only be made with biopsy. Immunophenotyping made with CD23+CD43+CD5+LEF-1 in the bone marrow biopsy showed a sensitivity of 95.45% (range, 84.53-99.44%) and a specificity of 100.00% (range, 85.75-100.00%) for CLL/SLL. Immunophenotyping made with CD23+CD43+CD5+CD200+ in FC showed a sensitivity of 100.00% (range, 91.96-100.00%) and a specificity of 82.61% (range, 61.22-95.05%) for CLL/SLL. Conclusion: This was the most extensive study to have compared immunophenotyping in IHC and FC in bone marrow biopsies of mature B cell leukemia/lymphoma. The addition of LEF-1 to the CD23(+), CD43(+), CD5(+) panel in IHC and the addition of CD200 to the same panel in FC will be extremely helpful in the differential diagnosis of typical/atypical CLL/SLL from mature B cell leukemia/lymphoma.

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Section: Resultscontrasting

confidence: 63%

A Comparison of Bone Marrow Flow Cytometry Findings and Bone Marrow Biopsy İmmunohistochemical Findings in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Methodological Study

Özdemir

Yavaşoğlu

Şenol

et al. 2023

esmj

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“…al reported LEF-1 expression in B-cell lymphocytosis previously (11). Recently, we have established that LEF1 is a highly specific marker for the diagnosis of B-CLL (26) and/ or LEF1 expression is related to atypical CLL (27). In our study, CLL cases showed differences in oncogenic FL-LEF1 and ΔLEF1 variants leading to the instability between long and short transcript ratio.…”

Section: Discussionsupporting

confidence: 53%

Differential Expression of LEF1 Isoforms in Adult Lymphoid and Myeloid Malignancies

Fırtına¹,

Ng²,

Erbilgin³

et al. 2021

experimed

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Objective: Lymphoid enhancer-binding factor-1 (LEF1) is one of the key regulators of lymphocyte proliferation and its aberrant expression is a prognostic factor for lymphoid or myeloid malignancies. In this study, we focused on the expression of LEF1 isoforms in several hematological malignancies and found tissue-specific differential expression for the full-length (FL)-LEF1 gene and its tumor suppressor (∆LEF1) variant.Material and Method: Fifty-three leukemia/lymphoma patients were included in this study. Diagnostic samples of "lymphoid group" patients: Chronic Lymphoblastic Leukemia (CLL) (n=10), B-cell Acute Lymphoblastic Leukemia (B-ALL) (n=9) and "myeloid group" patients: Chronic Myeloblastic Leukemia (CML) (n=12), Acute Myeloid Leukemia (AML) (n=13), and Multiple Myeloma (MM) (n=9) were studied. Healthy bone marrow, peripheral blood cells, and CD34 positive cells were used as controls. Total (T) and FL-LEF1 transcript levels were examined by using quantitative real-time polymerase chain reaction (qRT-PCR). T and FL-LEF1 mRNA ratios were also evaluated for calculation of ∆LEF1.Results: LEF1 levels were significantly high in lymphoid malignancies, but MM and AML patients have decreased LEF1 levels. Although CLL patients have high FL-LEF1 levels, the ratio of the T/FL levels was significantly decreased. Conclusion:LEF1 is a proliferation factor for lymphocytes and not only its differential overexpression but also the ratio of T/FL isoforms seem to accompany leukemia progress.

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“…Although our approach is admittedly more complex, as it requires advanced gating skills, we propose that it is a valuable MRD detection method that can be utilized in clinical laboratories without the need for specialized reagents or devices. It is also worth noting that recent research has identified LEF-1, CD160, and CD180 as surface markers specific to, or at least, applicable to, atypical CLL 30 , 35 , 36 . It is anticipated that in the near future, a flow cytometry method applicable to a broader spectrum of CLL cases will be established.…”

Section: Discussionmentioning

confidence: 99%

The kappa/lambda ratio of surface immunoglobulin light chain as a valuable parameter for MRD assessment in CLL with atypical immunophenotype

Aruga,

Ikeda,

Matsushita

et al. 2024

Sci Rep

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In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10−4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10−4. We propose this method as an effective MRD assay.

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Downregulation of Lymphoid enhancer‐binding factor 1 (LEF‐1) expression (by immunohistochemistry and/ flow cytometry) in chronic Lymphocytic Leukemia with atypical immunophenotypic and cytologic features

Cited by 10 publications

References 29 publications

A Comparison of Bone Marrow Flow Cytometry Findings and Bone Marrow Biopsy İmmunohistochemical Findings in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Methodological Study

A Comparison of Bone Marrow Flow Cytometry Findings and Bone Marrow Biopsy İmmunohistochemical Findings in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Methodological Study

Differential Expression of LEF1 Isoforms in Adult Lymphoid and Myeloid Malignancies

The kappa/lambda ratio of surface immunoglobulin light chain as a valuable parameter for MRD assessment in CLL with atypical immunophenotype

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