scholarly journals t(6;8), t(8;9) and t(8;13) translocations associated with stem cell myeloproliferative disorders have close or identical breakpoints in chromosome region 8p11-12

Oncogene ◽  
1998 ◽  
Vol 16 (7) ◽  
pp. 945-949 ◽  
Author(s):  
Max Chaffanet ◽  
Cornel Popovici ◽  
Dominique Leroux ◽  
Michèle Jacrot ◽  
José Adélaïde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chromosome Region ◽  
Myeloproliferative Disorders

Characteristics and Outcomes of 38 Patients with Acute Myeloid Leukemia Evolving from Previous Well Characterized Myeloproliferative Disorder.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2705-2705
Author(s):  
Constantine S. Tam ◽  
Francis Giles ◽  
Jorge Cortes ◽  
Guillermo Garcia-Manero ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Chemotherapy ◽  
Supportive Therapy ◽  
Myeloproliferative Disorders ◽  
Complete Response ◽  
Cancer Center ◽  
High Dose ◽  
Cell Transplant ◽  
Radioactive Phosphorus ◽  
Poor Risk

Abstract Antecedent hematological disorder (AHD) is a known adverse prognostic factor for patients with AML. AHD, however, encompasses a range of diverse hematological disorders. The characteristics and outcome of AML evolving from myeloproliferative disorders (MPD) without features of dysplasia remain poorly defined. Between 08/73 and 01/06, 76 patients were treated at the MD Anderson Cancer Center for AML evolving from a previous MPD. Of these, 38 were excluded from further analyses: inadequate pathological information for confident diagnosis of MPD (n=15), concomitant myelodysplastic features (n=11), chronic myelomonocytic leukemia (n=4), and less than twelve months between MPD diagnosis and AML occurrence (n=8). Baseline characteristics of remaining 38 patients with well-characterized MPD: median age 51 years (range 24–70); male 61%; cytogenetics - diploid 86%, del20q 14%; splenomegaly 27%. Diagnoses by WHO classification: polycythemia vera 47%; myelofibrosis 24%; essential thrombocythemia 18%; chronic MPD unclassifiable 11%. MPD therapy: hydroxyurea in 87% (median 3 years exposure), alkylating agent in 16%, and radioactive phosphorus in 8% of patients. AML occurred a median of 111 months (range 22 – 376) after MPD diagnosis. Median age at AML diagnosis was 65 years (range 40–81); cytogenetics were poor risk (−5, −7, 11q23, or ≥3 abnormalities) in 50% and intermediate risk in others (including diploid in 28%). Median survival was 23 weeks after AML diagnosis, and was not significantly different between patients who received AML therapy and those who received supportive therapy only (p=0.33) (figure 1), or between patients with intermediate and poor risk cytogenetics (p=0.12). Twenty-four patients received standard or high-dose Ara-C based induction chemotherapy: complete response (CR) rate was 38%, but responses were short-lived with all patients relapsing within 37 weeks in the absence of stem cell transplantation. Two patients underwent non-myeloablative matched sibling stem cell transplant in first CR: one remain leukemia free at 70 weeks, and the second relapsed 22 weeks post transplant but responded to re-induction chemotherapy, and remains alive at 38 weeks. AML evolving from a previous MPD carries an adverse prognosis, with very poor results from conventional induction chemotherapy. Exploration of novel agents in this patient population as a first line therapy is warranted. Figure Figure

scholarly journals Differences among myeloproliferative disorders in the behavior of their restricted progenitor cells in culture

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 578-584 ◽  
Author(s):  
H Croizat ◽  
D Amato ◽  
DL McLeod ◽  
D Eskinazi ◽  
AA Axelrad
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Myeloproliferative Disorders ◽  
Hemopoietic Stem Cell ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Highly Sensitive ◽  
Common Observation ◽  
Normal Sensitivity ◽  
Hemopoietic Progenitor

Abstract We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU- C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.

scholarly journals Dysplastic Platelets and Circulating Megakaryocytes in Chronic Myeloproliferative Diseases. II. Ultrastructure of Circulating Megakaryocytes

Blood ◽  
1974 ◽  
Vol 43 (6) ◽  
pp. 811-820 ◽  
Author(s):  
Jorge E. Maldonado
Keyword(s):  
Electron Microscopy ◽  
Stem Cell ◽  
Light And Electron Microscopy ◽  
Myeloproliferative Disorders ◽  
Cell Disease ◽  
Chronic Myeloproliferative Disorders ◽  
Myeloproliferative Diseases ◽  
Cytogenetic Studies ◽  
Chronic Myeloproliferative Diseases

Abstract Small circulating megakaryocytes were identified in four patients with chronic myeloproliferative disorders, and their morphologic features by light and electron microscopy are described. The morphologic and cytogenetic studies suggest that at least some of these cells are truly mononuclear. The circulating megakaryocytes were associated with the presence of dysplastic platelets. Both findings are thought to represent involvement of the megakaryocytic-platelet line, probably as an expression of stem cell disease.

STAT5 and STAT5 Inhibitors in Hematological Malignancies

2020 ◽  
Vol 19 (17) ◽  
pp. 2036-2046
Author(s):  
Manlio Tolomeo ◽  
Maria Meli ◽  
Stefania Grimaudo
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Hematological Malignancies ◽  
Kinase Inhibitors ◽  
Myeloproliferative Disorders ◽  
Main Role ◽  
Cellular Functions ◽  
Hematopoietic Stem ◽  
Immunological Responses

The JAK-STAT pathway is an important physiologic regulator of different cellular functions including proliferation, apoptosis, differentiation, and immunological responses. Out of six different STAT proteins, STAT5 plays its main role in hematopoiesis and constitutive STAT5 activation seems to be a key event in the pathogenesis of several hematological malignancies. This has led many researchers to develop compounds capable of inhibiting STAT5 activation or interfering with its functions. Several anti-STAT5 molecules have shown potent STAT5 inhibitory activity in vitro. However, compared to the large amount of clinical studies with JAK inhibitors that are currently widely used in the clinics to treat myeloproliferative disorders, the clinical trials with STAT5 inhibitors are very limited. At present, a few STAT5 inhibitors are in phase I or II clinical trials for the treatment of leukemias and graft vs host disease. These studies seem to indicate that such compounds could be well tolerated and useful in reducing the occurrence of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia. Of interest, STAT5 seems to play an important role in the regulation of hematopoietic stem cell self-renewal suggesting that combination therapies including STAT5 inhibitors can erode the cancer stem cell pool and possibly open the way for the complete cancer eradication. In this review, we discuss the implication of STAT5 in hematological malignancies and the results obtained with the novel STAT5 inhibitors.

Prolonged Fluconazole Prophylaxis Is Not Required In Patients With Acute Leukemias Or Myelodysplastic/Myeloproliferative Disorders After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT): A Pair-Matched Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4543-4543
Author(s):  
Eolia Brissot ◽  
Xavier Cahu ◽  
Thierry Guillaume ◽  
Jacques Delaunay ◽  
Sameh Ayari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Myeloproliferative Disorders ◽  
Reduced Intensity Conditioning ◽  
Acute Leukemias ◽  
Number Of Patients ◽  
Candida Infections ◽  
Fluconazole Prophylaxis ◽  
Reduced Intensity

Introduction Invasive fungal infections (IFI) due to Candida and Aspergillus species remain a major complication of allo-SCT. In the myeloablative setting, previous studies have demonstrated that fluconazole, administered for 75 days after transplant (400 mg/d), in a prophylaxis setting, can allow for a decreased risk of gut GVHD and disseminated candida infections or candidiasis-related death, resulting in an overall survival benefit (Marr et al., Blood 2000). However, to our knowledge, there is currently no study, addressing the potential benefit of fluconazole prophylaxis in the setting of reduced-intensity conditioning (RIC) allo-SCT. Methods This retrospective study included 105 patients with acute leukemia (AML, n=55, ALL, n=11) or myelodysplastic/myeloproliferative disorders (MDS, n=24; myeloproliferative disorder n=15) who received an allo-SCT between January 2000 and December 2011. In this series, patients received one (n=105) or two (n=4) RIC allo-SCT and PBSC as stem cell source for all. Among these 109 procedures, we compared those cases receiving (n=53) or not (n=56) fluconazole prophylaxis after transplant. The post-transplant fluconazole prescription or not was at the discretion of the attending physician and was homogeneous for each physician. There were not significant differences between both groups in terms of gender, median age (fluco: 55 vs 57 years), median follow-up (fluco: 42 months (range: 19-76) vs 37 months (range: 11-124)), median year of transplant (fluco: 2008 (range: 2003-2011) vs 2009 (range: 2000-2011)), type of disease and disease status at time of transplant or type of donor. Results The median time of fluconazole administration (400mg/day) after transplant was 88 days (range: 7-324). Fluconazole was stopped only in 2 patients because of (reversible) liver cytolysis. Before day +100, only 2 Aspergillus infections were documented in the fluconazole group vs 4 in the non-fluconazole group (P=NS). No Candida infections (septicemia or cutaneous candidiasis) developed in the fluconazole group compared to 2 in the non-fluconazole group (P=NS). After day +100, Aspergillus infections were documented in 5 patients in the fluconazole group versus 3 in the non-fluconazole group (P=NS). The number of patients receiving pre-emptive or curative antifungal treatment (voriconazole, caspofungin or ambisome) after transplant was higher in the non-fluconazole group (52% of cases vs 34%, P=0.09). 3-year OS, DFS and NRM were similar between both groups (fluco: 42% vs 51%, P=0.42, fluco: 38% vs 46%, P=0.62, and fluco: 28% vs 23%, p=0.67). Also, there were no significant differences in term of cumulative incidences of acute grade II-IV GVHD (fluco: 27% vs 36%, P=0.29), acute grade III-IV GVHD (fluco: 21% vs 18%, P=0.42) or chronic GVHD (fluco: 47% vs 33%, P=0.67). Conclusion This is the first series reporting the comparison of the use or not of fluconazole as prophylaxis after RIC allo-SCT. Our results showed that the use of fluconazole has no impact in term of fungal infections or overall outcomes after RIC allo-SCT, suggesting that fluconazole is not required after RIC allo-SCT. Large prospective studies are warranted to further confirm this important therapeutic issue. Disclosures: Moreau: CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Mohty:Novartis: Honoraria, Research Support Other.

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