RESUMO
Nonossifying fibromas (NOFs) are benign bone tumors occurring in the second decade of life. Most of the NOFs are diagnosed incidentally on the basis of its presentation on plain radiographs where they typically appear as small, cortical osteolytic lesions with sclerotic margin. They are mostly asymptomatic but can result in pathologic fractures if the lesion involves more than 50% of bone diameter. They are mostly treated with curettage and bone grafting. But in challenging situations where the classical surgery has failed or there is impending fracture of the neck of femur, bone structural support is needed. We are discussing two cases diagnosed as NOFs of intracapsular femoral neck. Both cases underwent curettage of tumor followed by free vascularized fibular graft. Results in both the cases were very gratifying, with complete resolution of symptoms during 1 year of follow-up.
RESUMO
Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states. Cell state annotations were benchmarked against purified cell populations, and in-depth characterization of gene expression programs underlying hematopoietic differentiation was undertaken. Projection of single-cell transcriptomes from 175 samples spanning acute myeloid leukemia (AML), mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) revealed 11 subtypes involving distinct stages of hematopoietic differentiation. These included AML subtypes with notable lymphoid or erythroid lineage priming, challenging traditional diagnostic boundaries between AML, MPAL, and AEL. Quantification of lineage priming in bulk patient cohorts revealed specific genetic alterations associated with this unconventional lineage priming. Integration of transcriptional and genetic information at the single-cell level revealed how genetic subclones can induce lineage restriction, differentiation blocks, or expansion of mature myeloid cells. Furthermore, we demonstrate that distinct cellular hierarchies can co-exist within individual patients, providing insight into AML evolution in response to varying selection pressures. Together, precise mapping of hematopoietic cell states can serve as a foundation for refining disease classification in acute leukemia and understanding response or resistance to emerging therapies.
RESUMO
The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor and mature cell types. Leukemia hierarchy composition was associated with functional, genomic and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP and Intermediate. Critically, variation in hierarchy composition along the Primitive versus GMP or Primitive versus Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A seven-gene biomarker derived from the Primitive versus Mature axis was associated with response to 105 investigational drugs. Cellular hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.