About

Dr. Liming Bao is a professor of Clinical Pathology and Laboratory Medicine at Weill Cornell Medical College, Cornell University. His primary research interests are in the genetic and genomic profiling of hematologic neoplasms and the genetic abnormalities underlying congenital conditions. Dr. Bao is the president of the American Cytogenomics Conference, a national professional organization for cytogeneticists in the United States. He joined Cornell to serve as the Director of the Cytogenetic division in Pathology and Laboratory Medicine. His educational background includes a Ph.D. from the University of South Alabama, an M.S. and M.D. from Shanghai Medical College, Fudan University in China. Dr. Bao has received notable honors such as a postdoctoral training fellowship award from the National Institutes of Health in 1999 and recognition as a Hundred Talents by the Chongqing Municipal Government in China in 2012. He is board-certified by the American Board of Medical Genetics in both Clinical Cytogenetics and Clinical Molecular Genetics.

Research topics

• Genetics
• Medicine
• Biology
• Cancer research
• Endocrinology
• Chemistry
• Internal medicine
• Molecular biology

Selected publications

• Co-mapping clonal and transcriptional heterogeneity in somatic evolution via got-multi.

  Blood · 2025-11-03

  articleOpen access

  Abstract Somatic evolution drives cancer progression and therapy resistance. Underlying phenotypic progressions is the development of marked clonal heterogeneity in most cancers. However, deciphering the downstream molecular effects of clonal heterogeneity in primary cancer has been limited due to the inability to isolate subclones by standard methods. While single-cell RNA-sequencing (scRNA-seq) provides high-resolution mapping of heterogeneous cell states, it cannot link transcriptional programs to cancer-driving mutations in these individual cells. We and others developed methods to detect genotypes and their transcriptional outputs in single cells (e.g., Genotyping of Transcriptomes; Nature, 2019). However, these approaches have technical limitations to broadly profile numerous mutations, which is nonetheless required for clonally complex neoplasms. The existing approaches are also restricted to fresh or frozen samples, limiting the use of the widely available pathology formalin fixed paraffin embedded (FFPE) tissues. To address these challenges, we developed Genotyping of Transcriptomes for Multiple Targets and Sample Types, GoT-Multi, a next generation single-cell multi-omics method compatible with FFPE tissues that integrates multiplexed genotyping with transcriptomic profiling. GoT-Multi adapts a probe-based scRNA-seq method (Flex Fixed RNA Profiling, 10x Genomics) by including custom mutation-specific probes along with the standard transcriptional probes. Furthermore, we developed an ensemble-based machine learning pipeline, GoT-Multi-ML, that optimizes the genotyping calls by denoising technical artifacts. GoT-Multi-ML leverages multiple machine learning models to learn the non-linear patterns of the genotyping data features (e.g., reads per genotyping transcript, GC content of probes), agnostic to the whole transcriptomic data. We validated GoT-Multi via a cell line-mixing experiment using SK-BR-3 and MCF-7 cell lines. GoT-Multi detected the targeted mutations (HIST1H1C A24T and S100A10 A77V) in the expected cell line (MCF-7) with an average genotyping rate of 72% and accuracy of 97%.To define the impact of clonal evolution on phenotypic progression, we focused on a prototype of cancer evolution, the progression of chronic lymphocytic leukemia (CLL) to therapy-resistant large B-cell lymphoma (LBCL) called Richter Transformation (RT). We applied GoT-Multi to a unique cohort of primary nodal cryopreserved samples containing both CLL and LBCL components (n = 5). We targeted 18 mutations (1-6 targets per sample) with a 98% median accuracy. We observed heterogeneous cancer cell states, including proliferating, stress response and inflammatory (n = 51,465 cells). LBCL was enriched in proliferating and cyclin D2-elevated states, whereas CLL was associated with a stress response signature. GoT-Multi enabled us to reconstruct the clonal architectures, up to 4 distinct subclones per lymphoma, and their associated cell states. Differential gene expression between mutated and wildtype cells revealed that genetically heterogenous subclones, including those with SRRM2 and JUNB mutations and therapy resistance-associated mutations in PLCG2 and BTK, displayed enrichment in inflammatory cell states, upregulating TNF and interferon signaling genes while suppressing cell cycle-related genes. Conversely, other subclones with mutations in, e.g., IRF8, POU2F2, PRKDC were associated with MYC activation and/or enhanced proliferation. These findings suggested that heterogeneous genotypes may converge on similar downstream transcriptional cell states. In addition, TNF itself was overexpressed in the proliferative subclones, suggesting that TNF production from these subclones may enhance inflammatory signaling of the TNF-responsive subclones, indicative of crosstalk between subclones. Finally, we demonstrated the applicability of GoT-Multi to pathology archived FFPE tissues. We profiled 9 mutations with an accuracy of 98% in an FFPE RT sample (n = 2,140 nuclei), allowing us to detect 5 subclones and their associated cell states. In summary, co-mapping of clonal and cell state heterogeneity at single cell resolution through GoT-Multi suggested that heterogeneous subclonal genotypes may converge on similar downstream oncogenic pathways to enhance overall tumor fitness. We envision that the broad applicability of GoT-Multi may help uncover the molecular underpinnings of cancer progression and therapy-resistance across oncology.

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• Co-mapping clonal and transcriptional heterogeneity in somatic evolution via GoT-Multi

  Cell Genomics · 2025-10-11 · 2 citations

  articleOpen access

  Somatic evolution leads to clonal heterogeneity, which fuels cancer progression and therapy resistance. To decipher the consequences of clonal heterogeneity, we require a method that deconvolutes complex clonal architectures and their downstream transcriptional states. We developed Genotyping of Transcriptomes for multiple targets and sample types (GoT-Multi), a high-throughput, formalin-fixed paraffin-embedded (FFPE) tissue-compatible single-cell multi-omics for co-detection of multiple somatic genotypes and whole transcriptomes. We developed an ensemble-based machine learning pipeline to optimize genotyping. We applied GoT-Multi to frozen or FFPE samples of Richter transformation, a progression of chronic lymphocytic leukemia to therapy-resistant large B cell lymphoma. GoT-Multi detected heterogeneous cancer cell states with genotypic data of 27 mutations, enabling clonal architecture reconstruction linked with their transcriptional programs. Distinct subclonal genotypes, including therapy-resistant mutations, converged on an inflammatory state. Other subclones displayed enhanced proliferation and/or MYC program. Thus, GoT-Multi revealed that distinct genotypic identities may converge on similar transcriptional states to mediate therapy resistance.

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• Systematic Assessment of MYC by Fluorescence in situ Hybridization in Multiple Myeloma Identifies a High-Risk Population Independent of Other Risk Factors

  Clinical Lymphoma Myeloma & Leukemia · 2025-09-01

  article
  PublisherDOI

• t(14;22)(q32;q11) translocation involving IGH and IGL acquired at progression of splenic marginal zone lymphoma treated with rituximab, ibrutinib, and obinutuzumab

  Annals of Hematology · 2025-02-27

  articleOpen accessSenior author

  Translocations involving immunoglobin (IG) are common in B-cell neoplasms. These IG translocations lead to the disposition of the enhancer or promoter of an IG locus, typically IGH, to a proto-oncogene, resulting in the elevated expression of the cancer gene. IG fusions play an important role in the diagnosis, prognostication, and therapy selection of B-cell lymphomas. A t(14;22)(q32;q11) translocation involving IGH and IGL is rare in lymphomas. We report herein clinicopathological characteristics, response to treatment, and outcomes of a first splenic marginal zone lymphoma case with a t(14;22)(q32;q11) translocation involving IGH and IGL treated with rituximab, ibrutinib, and obinutuzumab. Studies of additional cases are needed to elucidate the potential role of the t(14;22) translocation in lymphomagenesis and prognostication.

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• P024: Updated efficacy and safety of SHR-A1811, an anti-HER2 antibodydrug conjugate, in heavily pretreated advanced solid tumors with HER2-expression or mutations: a global, multicenter, phase 1 study

  The Breast · 2025-02-01

  articleOpen access
  PublisherDOI

• Zanubrutinib and venetoclax as initial therapy for CLL/SLL with obinutuzumab triplet consolidation in patients with detectable minimal residual disease (BruVenG).

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and B cell lymphoma 2 inhibitors (BCL-2i) are essential therapeutic drug classes in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Synergy has been observed between BTKi and BCL-2i, which can offer a safe, effective, and all oral fixed duration regimen (Tam et al., 2022). Triplet regimens combining BTKi, BCL2i, and anti-CD20 demonstrate improvement in undetectable minimal residual disease (uMRD), with comparable response rates, similar survival outcomes, but with increased hematologic toxicity and infections as compared to BTKi/BCL2i doublets (Brown et al., 2025). Thus, anti-CD20 therapy may best be utilized within a response-adapted approach in order to maximize efficacy while minimizing toxicity. Here we report interim efficacy and safety data utilizing a response adapted approach for initial treatment of CLL/SLL pts (BruVenG). Methods Eligible patients (pts) had untreated CLL/SLL with treatment indications per International Workshop on CLL (IWCLL) 2018 guidelines. Enrolled pts had adequate organ, bone marrow, and performance status. All pts were treated with an initial 3 cycle (C) lead-in of 320mg, oral, once daily zanubrutinib (Z). Starting at C4, venetoclax (V) was escalated to an effective dose of 400mg, oral, once daily. Escalation followed standard prescriber guidelines based on tumor lysis syndrome (TLS) risk evaluated prior to C4. Pts continued on Z and V until C17. At C16, radiographic, peripheral blood (PB), and bone marrow (BM) assessments were performed. If pts were MRD4 in both the PB and BM at C16, defined as MRD levels <1x10-4 via clonoSEQ® (Adaptive Biotechnologies) they stopped Z and V at C17. If pts were MRD+ in either PB or BM, then obinutuzumab (O) was introduced at C17 following standard CLL dosing guidelines, continuing with Z and V for an additional 6 cycles. At C23, pts receiving consolidation repeated radiographic, PB, and BM assessments and stopped treatment regardless of response. The coprimary endpoints are C16 PB, BM, and overall best MRD4 rates. Key secondary endpoints include C16 response rates, 36-month progression free survival (PFS), 36-month overall survival (OS), 36-month time to next treatment (TTNT), 24- and 36-month PB MRD negativity rates, tumor lysis syndrome (TLS) reduction rates, and safety. Responses were graded per IWCLL 2018 guidelines. Results Between 5/2023 and 4/2025, 45 pts enrolled. The median age was 61 (range 33-83), 31 (69%) were male, 37 (82%) were white, 5 (11%) were black. At entry, 26 (57%) had Rai stage III/IV disease, 16 (36%) had nodes ≥5cm, and 13 (29%) were high risk for TLS defined per V prescribing information. Twenty (44%) had an unmutated IGHV gene, 26 (58%) had del13q, 14 (31%) had trisomy 12, 7 (16%) had del11q, 7 (17%) had del17p, 8 (18%) had del17p or TP53 mutations, and 18 (40%) had complex karyotype defined as ≥3 abnormalities, with 9 (20%) having ≥5 abnormalities. Median follow-up time on study was 13.1 months. At time of data cutoff, 37 pts were evaluable for a best response at C4 or later, and 20 pts completed at least C16. The best overall response rate was 97%. Twenty pts were evaluable for complete response (CR) and MRD after at least 16 cycles, 7 (35%) achieved a CR and 6 (30%) were MRD4 or better in the PB while 3 (15%) were MRD4 or better in both PB/BM. Nine pts completed triplet consolidation, 6 (67%) were in CR at C23 with 7 (78%) converting to at least MRD4 in the PB and 6 (67%) converting to at least MRD4 in both PB/BM. At time of data cutoff, no pts progressed or had died. Forty three pts recorded an adverse event (AE). The most common any grade AE that occurred in 20% or more pts were fatigue (56%), diarrhea (53%), hypertension (31%), nausea (27%), upper respiratory infection (27%), arthralgia (27%), bruising (24%), neutropenia (22%), thrombocytopenia (22%), and rash (20%). No atrial fibrillation was recorded. One pt discontinued study due to a grade 4 intracranial hemorrhage prior to V escalation and 1 pt discontinued V due to recurrent Grade 4 neutropenia but continue on study with Z. Conclusions Response adapted therapy as initial treatment for CLL/SLL is feasible, effective, and safe. Despite initial low rates of MRD4 with the oral doublet, consolidation with O based triplet therapy leads to high rates of uMRD. Updated results on efficacy and safety will be reported.

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• Structure-based design and synthesis of novel highly potent and selective KRASG12C inhibitors

  European Journal of Medicinal Chemistry · 2025-10-30

  article
  PublisherDOI

• MYC rearrangements with immunoglobulin genes as an independent prognostic factor of progression-free survival in newly diagnosed patients

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction: MYC rearrangement (MYC-R), especially those involving the immunoglobulin loci (IGL, IGH, and IGK), are drivers of MM and other malignancies. IGL::MYC has been associated with hyperdiploidy and inferior outcomes. Despite this, MYC is not part of the recommended fluorescence in situ hybridization (FISH) panel at diagnosis. We describe the clinical impact of MYC alterations in newly diagnosed MM (NDMM) and the MYC-R prevalence in systematic MYC assessment by FISH and genomic proximity mapping (GPM). Methods: The Multiple Myeloma Research Foundation CoMMpass (MMRF-NGS cohort) was used to assess the frequency and impact of MYC rearrangements (MYC-R) on progression-free survival (PFS). FISH using a MYC break apart probe was part of the routine FISH panel at our center for MM starting in June 2023 in 133 patients (pts) (WCM-FISH cohort). GPM was performed on CD138+-selected cells from 50 pts who part of a prospective clinical trial of NDMM (NCT01559935 (CarBiRD cohort)) and in 37 pts from the WCM-FISH cohort. MYC-R breakpoints and gain (MYC-g) were identified. PFS was defined as the time from MM diagnosis to progression of disease or death, as determined by the International Myeloma Working Group. High-risk cytogenetics (HR-CG) were defined as any of del17p, t(4;14), t(14;16), or gain1q. Supported by R44CA268681 and WA Care Fund. Results: In the MMRF-NGS cohort, MYC-R was seen in 234/913 pts (25.6%), with most MYC-R having IGH/IGL/IGK (IG::MYC) as a partner in 52% of cases. IG::MYC pts had inferior PFS (25.4 months) when compared to MYC-R with non-IGH/L/K partners (MYC::non-IG) (42.2 months, pairwise p= 0.04) and MYC-negative (neg) (37.9 months, pairwise p= 0.04). There were no differences in PFS between MYC-neg and MYC::non-IG (p = 0.59). In a multivariable model, IG::MYC remained associated with inferior PFS (hazard ratio [HR] 1.39, 1.09-1.7, p = 0.01) after adjusting for age, transplant, triplet vs. duplet induction, and del17p, gain1q, del1p, and del13q status. 24 pts with IG::MYC had sequential samples available, and 22/24 (92%) IG::MYC was present at diagnosis, suggesting IG::MYC-Ris a truncal event and is often present at MM diagnosis. In the WCM-FISH cohort, MYC alterations were present in 44/133 pts with MM (33%). MYC-R was present in 35 pts (26%), while MYC-g was present in 13 (9.8%). Pts with MYC-R had significantly shorter PFS compared to MYC-neg (15.6 vs. 35.7 months, p = 0.017). Other variables associated with PFS included ISS, R-ISS, lactate dehydrogenase, albumin, del17p, and HR-CG. In the multivariable model, only MYC-R was associated with inferior PFS (HR 2.82, 95% CI 1.12-7.06, p = 0.02). When pts were stratified by MYC-R and HR-CG status, pts with MYC -R and no HR-CG had inferior PFS compared to MYC-neg/no HR-CG pts (p = 0.001) and had comparable PFS to HR-CG alone. Most MYC-R cases were not further assessed by standard FISH for, with MYC::IGH being the only partner genes identified (3/35 cases). In the CarBiRD cohort, GPM identified 17/50 (34%) pts with MYC alterations, including 12 pts (24%) with MYC-R. The MYC partner was identified in all cases, with 8 pts having IG::MYC. MYC-R, were associated with inferior PFS when compared to MYC-neg (HR 2.1, 1.06 – 4.4, p = 0.03), mainly driven MYC::IG cases, which had inferior PFS when compared to non-MYC-R pts (HR 4.27, 1.82 – 10.1, p < 0.001). In the pts who had GPM and FISH available (87 pts), GPM identified MYC alteration in 32/87 (37%) of cases, including MYC-R in 27/87 (31%) of pts. 48% of MYC-R involved the IGL, IGK or IGH (6, 4, and 3 cases, respectively). GPM identified the breakpoint in all cases, also identifying complex alterations involving several translocations or inversions in the same patient in addition to inversions of chromosome 8q. GPM detected all cases of t(11;14), t(4;14), MYC-R, and t(14;16) identified by FISH, in addition to 3 pts with t(11;14), t(14;16), and MYC-R that FISH missed due to atypical breakpoints. MYC alterations were associated with a higher rate of del1p, hyperdiploidy, and del17p, while mutually exclusive from t(11;14). Conclusion: MYC-R is common in NDMM and is associated with inferior PFS independent of other genomic variables. MYC FISH should be considered part of the standard risk stratification. MYC partner may have important prognostic implications. GPM provides higher resolution and can locate other recurrent abnormalities in MM, in addition to characterizing complex MYC alterations and breakpoints.

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• A case of testicular diffuse large B-cell lymphoma with late relapse in the skin: the critical role of comparative phenotypic, clonality, and cytogenetic testing

  Leukemia & lymphoma/Leukemia and lymphoma · 2024-07-17 · 1 citations

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• Near-tetraploidy/tetraploidy acute myeloid leukemia with clinical, pathologic and molecular characteristics

  Leukemia & lymphoma/Leukemia and lymphoma · 2024-07-25 · 2 citations

  article

  was the most common molecular mutation associated with NT/T AML (44.5%). Of the patients receiving treatment for NT/T AML, 80% achieved a CR. The median overall survival for the entire cohort was 4.5 months.

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Frequent coauthors

• Yi Huang

  Sun Yat-sen Memorial Hospital

  67 shared

• Guowei Lin

  Shangrao Normal University

  46 shared

• Richard D. Irons

  American Chemistry Council

  42 shared

• Ling Lu

  36 shared

• Ling Lv

  Fudan University

  33 shared

• Sherilyn A. Gross

  32 shared

• Hengjuan Sun

  30 shared

• Meihua Yang

  28 shared

Awards & honors

• Postdoctoral training fellowship award, National Institutes…
• Hundred Talents, Chongqing Municipal Government, China (2012…
• President of American Cytogenomics Conference