ASH 2024 | Synchronous dual hematologic malignancies of both myeloid and lymphoid lineage

Yeah, this is an interesting study that we undertook. So myeloid neoplasms and lymphoid neoplasms are genetically and pathobiologically thought to be distinct from each other. However, there are a lot of genetic mutations that are recurrent in both myeloid and lymphoid side of things. Also, there is an entity called mixed phenotype acute leukemia where we see the same genetic markers driving a disease which has blasts that are expressing both myeloid and lymphoid markers on it. So we utilize the power of single-cell sequencing to try to see if we can find a common clonal origin between myeloid and lymphoid neoplasms. We had, this is a very expensive technology, so we had about 20 samples that we analyzed and some of them were sequential. There were different combinations of myeloid and lymphoid malignancies. There was MDS, AML, or MPN on the myeloid side, whereas on the lymphoid side we had lymphoplasmacytic lymphoma or CLL or multiple myeloma as a representative diagnosis. We looked at it in both ways. We looked at it in clinical outcomes and we clearly showed that looking at our institutional database, patients with synchronous dual heme malignancies, so myeloid and lymphoid together, had a worse outcome compared to myeloid malignancies alone. And they had a lot of mutations in higher incidence like SF3B1 or TP53 compared to myeloid malignancy alone. And then when we did the single-cell work, what we found is the dominant clone was equitably distributed across different cell subpopulations in these disease samples, you know, in myeloid, lymphoid, and hematopoietic stem and progenitor cell populations as well. So our hypothesis was that we could possibly link these two different malignancies into a common clonal origin and we actually found some dominant clones that were distributed both in progenitor or mother cells and the myeloid and lymphoid cells in these samples of synchronous dual heme malignancies which points towards common clonal origin as well. The next part of the study what we did is we looked into again in the single-cell level we looked into the expression of different phenotypic markers or CD markers that are used to designate these myeloid and lymphoid disease subtypes. And what we saw interestingly is there were a lot of overlap between those two subpopulations of those markers, which again points towards similarity of this disease state with the mixed phenotype acute leukemia that I described earlier, that not only they are genomically linked, that actually translates into phenotypic marker sharing as well, which altogether speaks towards considering synchronous dual-heme malignancy as potentially a single disease entity in future studies.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.