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Updated: Jun 12, 2025
From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
Whole-genome sequencing reveals cellular origin of concomitant chronic lymphocytic leukemia and multiple myeloma: a
Jianing Zhang1, Ji Ma2, Ying Li3
1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Insights
This study reveals that chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) can originate from the same B cell precursor. Whole-genome sequencing clarifies their clonal relationship and distinct differentiation pathways.
Area of Science:
- Hematology
- Genomics
- Oncology
Background:
- Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are B cell malignancies.
- The clonal relationship between CLL and MM is often unclear, hindering understanding of their pathogenesis.
Purpose of the Study:
- To investigate the clonal relationship between synchronous CLL and MM in a rare clinical case.
- To elucidate the B cell differentiation pathways involved in the development of both malignancies.
Main Methods:
- Whole-genome sequencing (WGS) of malignant lymph node (LN) and bone marrow (BM) tissues.
- Analysis of single nucleotide variants (SNVs), significantly mutated genes (SMGs), and copy number variations (CNVs).
- Assessment of B cell receptor (BCR) IGH rearrangement and light-chain expression.
Main Results:
- High consistency in SNVs, SMGs, and CNVs between CLL and MM samples.
- Distinct BCR IGH rearrangement features and light-chain expression patterns observed.
- Evidence suggests a common origin from hematopoietic stem cells/progenitors.
Conclusions:
- CLL and MM in this patient originated from the same progenitor cell.
- Oncogenic mutations occurred at different B cell differentiation stages.
- WGS is a valuable tool for exploring malignant B cell genesis.
Abstract:
Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are hematological disorders affecting B cells. The clonal relationship between CLL and MM has not always been clarified, although this information is critical to understanding its pathogenesis. Here, we present a rare clinical case of synchronous CLL and MM. Whole-genome sequencing (WGS) was performed using malignant lymph node (LN) and bone marrow (BM) tissues. Based on the high consistency of single nucleotide variants (SNVs), significantly mutated genes (SMGs), copy number variations (CNVs), different B cell receptor (BCR) IGH rearrangement features in LN and BM, and the different light-chain expression patterns in CLL and MM cells, we concluded that CLL and MM cells from this patient originated from the same hematopoietic stem cell/progenitors, different pro-B cells and suffered oncogenic mutations at different B cell differentiation stages. Depth analysis of genome features using WGS provides a new method to explore the process of malignant B cell genesis.
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