CML Session Summaries from EHA2026 Congress - Day 4

18 June 2026
Type: Events
Photo_EHA2026 Congress

June 2026 - We're bringing you highlights from the EHA2026 Congress with summaries of selected scientific sessions on CML.

Oral Session: Biology and Translational Research

Session summary

This session highlighted major advances in understanding the biological mechanisms underlying disease progression and treatment resistance in CML. Using single-cell technologies, genomic and transcriptomic profiling, and functional studies, investigators provided new insights into the origins of blast crisis, identified biomarkers capable of detecting high-risk chronic phase disease before transformation, uncovered mechanisms of resistance to asciminib, and refined the biological classification of accelerated phase CML. Together, these findings emphasise that disease progression begins long before overt blast crisis develops and demonstrate how translational research may enable earlier intervention and more personalised treatment strategies.

Our key takeaways from the presentations:

Presentation 1

Single-cell genetic lineage tracing reveals pre-existing blast crisis-initiating clones at chronic-phase CML diagnosis

Speaker: Elaine Cao (Singapore)

‘Lymphoid and myeloid blast crisis follow distinct evolutionary routes’

Key points:

  • Blast crisis clones originate during chronic phase: In 6 of 7 patients, the cell of transformation could be traced back to chronic phase disease, demonstrating that progression-associated clones are already present months to years before overt blast crisis develops. The single exception was a patient with a germline TP53 background, in whom the relevant clones were not detectable in chronic phase.
  • Different origins for lymphoid and myeloid blast crisis: The cell of transformation was consistently identified as Pro-B cells in lymphoid blast crisis, whereas myeloid blast crisis originated from more primitive HSC/MPP populations with multilineage involvement. 
  • Blast crisis signatures are already detectable at diagnosis: Established blast crisis transcriptional programs were confirmed in all three lymphoid cases and in three of four myeloid cases, indicating that transformation-associated programs emerge early.
  • Inflammatory pathways are a common feature: NF-κB-driven inflammatory signatures were consistently enriched in all three lymphoid blast crisis cases and in three of four myeloid blast crisis cases, suggesting inflammation as a common driver of progression. This inflamed progenitor state was described as a feature of the transforming clone not previously characterised.
  • Myeloid transformation is biologically heterogeneous: Unlike the convergent lymphoid pathway, myeloid blast crisis displayed diverse genetic alterations and more variable transcriptional programs.
  • Single-cell lineage tracing overcomes limitations of bulk analyses: Simultaneous assessment of copy number alterations, somatic mutations and gene expression at single-cell resolution enabled direct identification of transformation-initiating clones.

Presentation 2

Single-cell transcriptomic-guided flow cytometric analysis of inflamed megakaryocytic and lymphoid progenitors at diagnosis identifies chronic-phase CML at high risk for blast crisis transformation

Speaker: S. Tiong Ong (Singapore)

‘Single-cell omics can be translated into clinically useful tests.’

Key points:

  • Single-cell omics enabled development of protein-based biomarkers: Transcriptomic analyses identified lineage-specific inflammatory signatures that were translated into practical multiparameter flow cytometry assays.
  • Distinct progenitor expansion patterns predict transformation: Patients progressing to lymphoid blast crisis demonstrated lymphoid progenitor expansion, while both lymphoid and myeloid blast crisis patients showed expansion of megakaryocytic progenitors.
  • Inflammation precedes cellular expansion: Phospho-STAT1-positive inflammatory signals in progenitor cells were detectable before overt expansion, suggesting that inflammatory activation may be an early event in transformation.
  • Flow cytometry identified high-risk patients with high accuracy: The optimised assay achieved 95–100% sensitivity and over 90% specificity in the most recent validation cohort. The assay was statistically superior to the Sokal score and trended to superiority over the ELTS score, and is positioned as complementary to ELTS rather than a replacement.
  • Very high-risk patients may benefit from earlier intervention: Earlier identification could allow more intensive monitoring, use of more potent TKIs and timely referral for transplantation before blast crisis develops.
  • More potent frontline TKIs may be preferable in selected patients: The data suggested that patients with isolated MKP expansion without accompanying inflammatory signalling (phospho-STAT1 negative) may particularly benefit from second-generation or later TKIs frontline.

Presentation 3

Influence of non BCR::ABL1 somatic mutations on tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia

Speaker: Michele Ciboddo (Helsinki)

‘Not all resistance mechanisms are shared across TKIs – BCOR loss confers resistance to asciminib but not to imatinib.’

Key points:

  • CROP-seq identified pathways associated with primary TKI resistance: Single-cell CRISPR screening revealed transcriptional signatures involving mTOR signalling, unfolded protein response and apoptosis regulation.
  • BCOR loss specifically mediates asciminib resistance: BCOR knockout cells retained sensitivity to imatinib but became resistant to asciminib, highlighting a mutation-specific resistance mechanism.
  • Findings were validated experimentally: The differential sensitivity pattern was reproducible in the K562 cell-line model used throughout.
  • BCL-XL emerged as a key mediator: BCOR-deficient cells displayed higher baseline BCL-XL protein levels and maintained elevated expression after asciminib treatment.
  • Combination therapy restored sensitivity: BCOR knockout cells showed increased susceptibility to combined treatment with asciminib and the oral BCL-XL inhibitor A-1331852.
  • Results may guide future therapeutic strategies: Understanding mutation-specific resistance mechanisms could enable rational combination approaches to overcome resistance.

Presentation 4

Molecular mechanisms of ZDHHC19-mediated JAK1 palmitoylation driving TKI resistance in CML leukemia stem cells

Speaker: Teng Wang (Chongqing)

‘Metabolic rewiring through JAK1 palmitoylation represents a novel therapeutic vulnerability in TKI-resistant CML.’

Key points:

  • Alterations in the bone marrow adipocyte compartment were observed in CML: Patients demonstrated reduced adipocyte numbers and increased circulating palmitic acid levels, particularly in TKI-resistant disease.
  • Palmitic acid promoted TKI resistance in leukemia stem cells: Functional experiments showed enhanced resistance following exposure to palmitic acid.
  • Resistance was mediated through protein palmitoylation: Elevated palmitoyl-CoA levels promoted activation of the JAK1–STAT3 pathway rather than simply serving as an energy source.
  • ZDHHC19 was identified as the responsible enzyme: Integrated transcriptomic and palmitoylation analyses identified ZDHHC19 as a key regulator of JAK1 palmitoylation, with ZDHHC19 knockdown reducing JAK1 palmitoylation and downstream STAT3 activation.
  • Blocking palmitoylation restored TKI sensitivity: Inhibition with the broad-spectrum palmitoylation inhibitor 2-bromopalmitate reduced proliferation, induced apoptosis and improved responses in mouse models. Enzyme specificity was supported separately by the ZDHHC19 knockdown experiments above rather than by 2-bromopalmitate alone.
  • Targeting lipid metabolism may represent a new therapeutic avenue: Development of selective ZDHHC19 inhibitors may offer novel strategies to eradicate resistant leukemia stem cells.

Presentation 5

Integrated genomic and transcriptomic analyses reveal biological heterogeneity of accelerated-phase chronic myeloid leukemia and 
identify a blast-phase like subgroup

Speaker: Xiaoshuai Zhang (Beijing)

‘Evolved accelerated phase spans a biological continuum between chronic phase and blast phase.’

Key points:

  • De novo accelerated phase resembles newly diagnosed chronic phase: Genomic and transcriptomic analyses demonstrated that de novo AP shares features with chronic phase rather than blast phase disease.
  • Clinical AP features do not necessarily indicate blast-phase biology: Even blast-enriched AP subtypes remained molecularly distinct from de novo blast phase.
  • Evolved AP represents a biological continuum: Patients with evolved AP exhibited characteristics intermediate between TKI-resistant chronic phase and blast phase disease.
  • Two molecular subgroups were identified: Transcriptomic profiling separated evolved AP into CP-like AP and BP-like AP subgroups.
  • BP-like AP was associated with poor prognosis: Patients with BP-like AP had outcomes similar to blast phase CML and significantly worse survival than CP-like AP patients.
  • BP-like AP was characterised by genomic instability and stemness activation: Increased mutational burden, leukemia stem-cell signatures and activation of cell cycle and DNA repair pathways distinguished this subgroup.
  • Analysis was performed on bulk RNA-seq of total leukocytes rather than sorted blasts, and blast-phase patient numbers were limited.