Elisa Dorantes-Acosta

Expression of CD90, CD96, CD117, and CD123 on Different Hematopoietic Cell Populations from Pediatric Patients with Acute Myeloid Leukemia

BACKGROUND AND AIMSnIn trying to contribute to our knowledge on the biology of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) from pediatric acute myeloid leukemia (AML), in the present study we analyzed the expression of four cell surface antigens relevant to human hematopoiesis-CD90, CD96, CD117, and CD123-in bone marrow from pediatric AML patients and normal control subjects.nnnMETHODSnCD34(+) CD38(-) cells (enriched for HSC) and CD34(+) CD38(+) cells (enriched for HPC) were resolved on the basis of CD34 and CD38 expression. Concomitantly, expression of CD90 and CD96 or CD117 and CD123 was assessed by multicolor flow cytometry in each cell population.nnnRESULTSnCD90 and CD117 were expressed in a low proportion of CD34(+) CD38(-) and CD34(+) CD38(+) cells and no significant differences were observed between normal marrow and AML at diagnosis. In contrast, CD96(+) cells and CD123(+) cells were found at significantly higher levels in both cell populations from AML at diagnosis, as compared to normal marrow. Levels of both cell surface markers after treatment remained higher than in normal marrow.nnnDISCUSSIONnThese results show an increased frequency of CD96(+) and CD123(+) cells within the CD34(+) cell population from pediatric AML; this is consistent with the findings reported previously for adult AML. Our study supports the notion that expression of such antigens should be explored for their use as markers for diagnosis and prognosis.

Adult, but not neonatal, human lymphoid progenitors respond to TLR9 ligation by producing functional NK-like cells

Remarkable progress has been made in characterizing factors controlling lineage fate decisions of primitive progenitors that initiate the lymphoid program in bone marrow. However, the understanding of neonatal/adult differences in environmental signals that influence differentiation pathway stability is still incomplete. Our recent findings suggest that Toll-like receptors provide a mechanism for producing cells of the innate immune system from early stages of lymphoid development in mice. We now show that both human early multilymphoid progenitors and more differentiated lymphoid progenitors from normal adult bone marrow express TLR9. Furthermore, they respond to its ligation by upregulating the expression of IL-15Rβ (CD122) and accelerating the production of functional natural killer (NK)-like cells. Proliferation of the presumed equivalent progenitor cells from umbilical cord blood was stimulated by CpG-containing oligonucleotides or herpes simplex virus, but the already robust NK-cell formation was unchanged. This new information adds to other known differences between neonatal and adult lymphoid progenitors and suggests only the latter replenish innate NK-like cells in response to Toll-like receptor agonists.

T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% and 25% of total childhood and adult ALL cases, respectively. During T-ALL, patients are at risk of organ infiltration by leukemic T-cells. Infiltration is a major consequence of disease relapse and correlates with poor prognosis. Transendothelial migration of leukemic cells is required to exit the blood stream into target organs. While mechanisms of normal T-cell transmigration are well known, the mechanisms of leukemic T-cell extravasation remain elusive; but involvement of chemokines, integrins and Notch signaling play critical roles. Here, we summarize current knowledge about molecular mechanisms of leukemic T-cell infiltration with special emphasis on the newly identified subtype early T-cell-progenitor (ETP)-ALL. Furthermore, we compare the extravasation potential of T-ALL cells with that of other hematologic malignancies such as B-ALL and acute myeloid leukemia (AML).

Early Hematopoietic Differentiation in Acute Lymphoblastic Leukemia: The Interplay Between Leukemia-Initiating Cells and Abnormal Bone Marrow Microenvironment

By virtue of their self-renewal and tightly regulated multi-lineage differentiation properties, hematopoietic stem cells (HSCs) generate the whole blood system throughout postnatal life. During malignant hematological disorders, including acute leukemias, a number of intrinsic and extrinsic cues influence the hematopoietic differentiation pathway and cooperate to make aberrant cell fate decisions concomitant with cell transformation. The cellular origin of these disorders is a fundamental matter in question. In keeping with the hierarchical model of tumor evolution, a conspicuous and unique leukemic stem cell (LSC) population is most likely the foundation of acute and chronic myeloid leukemias. In contrast, all B-cell differentiation stages in acute lymphoblastic leukemia (ALL) function as leukemia-initiating cells (LICs), are endowed with primitive stem cell properties and are apparently responsible for the long-term maintenance of tumor growth within the bone marrow (BM) and for relapse of the disease following remission. Furthermore, LICs reveal the ability to create irregular BM microenvironments that may result in proinflammatory scenarios with a permissive role by allowing leukemic cell development at the expense of normal hematopoiesis. This chapter outlines the recent findings contributing to the understanding of malignant hematopoiesis through the biology of early stem and progenitor cells in the context of abnormal microenvironments within leukemic BM. By unraveling the role of leukemic precursor cells in the initiation of local inflammatory processes leading to hematopoietic instability, we may learn about additional mechanisms co-participating in the etiology and maintenance of this pathological condition.

Thymidine Kinase: A Biomarker for Recently Diagnosed Acute Leukemia in Pediatric Patients According to the Cell Line Involved

BACKGROUND AND AIMSnAcute leukemia (AL) is a heterogeneous group of diseases characterized by a disorganized clone proliferation of hematopoietic cells. Thymidine kinase (TK) is a cell enzyme involved in DNA synthesis and is considered a cellular proliferation marker in some solid tumors.nnnMETHODSnA cross-sectional prospective and comparative study was performed in the Federico Gomez Childrens Hospital in Mexico (HIMFG, in Spanish) in 125 samples of patients of the HIMFG with AL and 138 samples of children without leukemia. Serum TK levels were determined for both groups.nnnRESULTSnOf the children with AL, 90 presented B-cell acute lymphoblastic leukemia (B-ALL); 13, T-cell acute lymphoblastic leukemia (T-ALL); and 22, acute myeloid leukemia (AML). A median (m) TK level of 23.7 IU (IQR 17-35.7) was observed in the group without AL and 91 IU (IQR 98-392) in the AL group. This difference was statistically significant (p <0.0001). When analyzing TK levels according to the type of leukemia, the m was as follows: 68 IU (IQR 35-118) for B-ALL, 470 IU (IQR 88-750) for AML, and 1678 IU (IQR 288-2108) for T- ALL.nnnCONCLUSIONnTK is an enzyme showing heterogeneous levels in B-ALL although it is significantly increased in 90% of patients with T-ALL and AML.