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David P Steensma

Publications and source records attributed to David P Steensma.

At least 19 recordsLinked to original sources
PubMed2003

Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations.

Acquired somatic mutations in ATRX, an X-linked gene encoding a chromatin-associated protein, were recently identified in 4 patients with the rare subtype of myelodysplastic syndrome (MDS) associated with thalassemia (ATMDS). Here we describe a series of novel point mutations in ATRX detected in archival DNA samples from marrow and/or blood of patients with ATMDS by use of denaturing high-performance liquid chromatography (DHPLC), a technique sensitive to low-level mosaicism. Two of the new mutations result in changes in amino acids altered in previously described pedigrees with germ line ATRX mutations (ATR-X syndrome), but the hematologic abnormalities were much more severe in the patients with ATMDS than in the corresponding constitutional cases. In one ATMDS case where DNA samples from several time points were available, the proportion of ATRX-mutant subclones correlated with changes in the amount of hemoglobin H. This study strengthens the link between acquired, somatic ATRX mutations and ATMDS, illustrates how molecular defects associated with MDS and other hematologic malignancies masked by somatic mosaicism may be detected by DHPLC, and shows that additional factors increase the severity of the hematologic phenotype of ATRX mutations in ATMDS.

Aged↗
PubMed2003

Deletion of the alpha-globin gene cluster as a cause of acquired alpha-thalassemia in myelodysplastic syndrome.

Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of alpha-thalassemia (alpha-thalassemia in myelodysplastic syndrome [ATMDS]) characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling gene, have recently been found in 12 patients with typical features of ATMDS, though they have not been detected in MDS patients with similar red blood cell findings but little HbH. The alpha-globin genes themselves have appeared normal in all ATMDS patients studied to date. Here we characterize the molecular defect in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost a greater than 1.9-Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both alpha-globin genes. Red blood cell changes associated with this acquired somatic genotype (--/alpha alpha) are surprisingly severe, demonstrating that a minor globin chain imbalance may be unexpectedly deleterious during the abnormal erythropoiesis that occurs in the context of MDS.

Aged↗
PubMed2003

The narrow path.

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Attitude of Health Personnel↗
PubMed2003

Why me?

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Adaptation, Psychological↗
PubMed2003

The myelodysplastic syndrome(s): a perspective and review highlighting current controversies.

The myelodysplastic syndrome (MDS) includes a diverse group of clonal and potentially malignant bone marrow disorders characterized by ineffective and inadequate hematopoiesis. The presumed source of MDS is a genetically injured early marrow progenitor cell or pluripotential hematopoietic stem cell. The blood dyscrasias that fall under the broad diagnostic rubric of MDS appear to be quite heterogeneous, which has made it very difficult to construct a coherent, universally applicable MDS classification scheme. A recent re-classification proposal sponsored by the World Health Organization (WHO) has engendered considerable controversy. Although the precise incidence of MDS is uncertain, it has become clear that MDS is at least as common as acute myelogenous leukemia (AML). There is considerable overlap between these two conditions, and the former often segues into the latter; indeed, the distinction between AML and MDS can be murky, and some have argued that the current definitions are arbitrary. Despite the discovery of several tantalizing pathophysiological clues, the basic biology of MDS is incompletely understood. Treatment at present is generally frustrating and ineffective, and except for the small subset of patients who exhibit mild marrow dysfunction and low-risk cytogenetic lesions, the overall prognosis remains rather grim. In this narrative review, we highlight recent developments and controversies within the context of current knowledge about this mysterious and fascinating cluster of bone marrow failure states.

Combined Modality Therapy↗
PubMed2003

Clonal cytogenetic abnormalities in bone marrow specimens without clear morphologic evidence of dysplasia: a form fruste of myelodysplasia?

Cytogenetic abnormalities suggestive of a myeloid disorder are occasionally observed in the bone marrow (BM) cells of patients with morphologically and immunohistochemically unremarkable marrow aspirates and biopsies. Between 1994 and 2000, 55 such patients were seen at our institution (34 men; median age of 66 years). The indications for BM sampling included unexplained cytopenias (31 patients), staging or follow-up of a lymphoproliferative disorder or a plasma cell dyscrasia (18 patients), or another miscellaneous reason (6 patients). Specific cytogenetic abnormalities included a 20q deletion or monosomy 20 (10 patients), a chromosome 7 deletion (8 patients), +8 (5 patients), del(5q) or a 5q translocation (4 patients), and del(13q) (2 patients). Eleven patients had a complex karyotype. As of January 2002, 23 of the 55 patients were dead; median follow-up for living patients is 20 months. Of the 23 dead patients, 1 died of acute myelogenous leukemia (AML) and 6 of complications related to cytopenias. This study provides support for obtaining cytogenetic studies in patients with unexplained cytopenias if a morphologic explanation for the cytopenias is lacking. Continued follow-up of this heterogeneous cohort and further studies of similar patients will more clearly define the disease processes and prognosis for this constellation of laboratory findings.

Aged↗
PubMed2003

Splenic histopathological patterns in chronic myelomonocytic leukemia with clinical correlations: reinforcement of the heterogeneity of the syndrome.

The syndrome of chronic myelomonocytic leukemia (CMML) includes a heterogeneous group of patients who exhibit both myelodysplastic and myeloproliferative clinicopathological features. Troublesome splenomegaly is uncommon in myelodysplastic syndrome (MDS), but when organomegaly occurs, this complication is more likely to be associated with myelodysplastic-myeloproliferative overlap syndromes such as CMML rather than "dysplasia-only" MDS types such as refractory anemia. We report a single-institution experience with splenectomy in CMML patients, including a detailed review of splenic histopathology. Twelve patients with CMML underwent splenectomy at the Mayo Clinic, primarily because of refractory thrombocytopenia and/or mechanical complications related to splenomegaly. Three of the 12 patients (25%) died as a direct result of surgery, and significant postoperative morbidity was seen in another 4 patients (33%). Thrombocytopenia improved in 4 of the 11 patients (36%) with low platelet counts before surgery. Three of the four responders had an abundance of CD68 (PGM1)-positive foamy histiocytes in the marginal zone surrounding the splenic white pulp-a pattern which can be seen in immune thrombocytopenia-and two of these three patients had thrombocytopenia out of proportion to the degree of anemia pre-operatively, suggestive of peripheral destruction of platelets. More consistent splenic pathological findings in the 12 patients included trilineage extramedullary hematopoiesis in splenic red pulp and expansion of splenic cords by a myelomonocytic infiltrate. This study underscores both the uniformity and diversity of splenic findings in CMML, highlights the potential dangers and benefits of splenectomy in this group, and suggests peripheral destruction of platelets as a mechanism contributing to thrombocytopenia in a subset of CMML patients.

Adult↗
PubMed2003

"Pawn Ball Megakaryocytes": from the marvellous medici and dear Old Saint Nick to the unsanctified marrow of myelodysplasia.

The worlds of biology and medicine in general, and the discipline of hematology in particular, enjoy a rich lexicon full of fascinating etymologies. The term "Pawn Ball Megakaryocytes" has been used to describe a peculiar type of abnormal cell that can be found in bone marrow samples taken from some patients with the myelodysplastic syndrome (MDS). The three-ball pawnbroker's symbol that these megakaryocytes resemble is ancient and may have derived from the insignia of the Medici family or the symbol of Saint Nicholas of Myra. The murky history of the symbol and its significance for myelodysplasia are reviewed.

Bone Marrow Examination↗
PubMed2003

The kiss of death: a severe allergic reaction to a shellfish induced by a good-night kiss.

True (IgE-mediated) allergic reactions to crustaceans are relatively common and can be serious. A young woman with a clinical history of multiple urticarial reactions after touching shrimp and lobster dishes was seen in an emergency department of a Mayo Clinic-affiliated hospital for an anaphylactic reaction that developed immediately after she kissed her boyfriend. The boyfriend had eaten several shrimp just before the kiss. It is important to warn susceptible patients that food does not actually have to be eaten to trigger an allergic reaction; touching the offending food and kissing or touching someone who has recently eaten the food can be enough to cause a major reaction.

Adult↗
PubMed2003

The chronic myeloproliferative disorders: an historical perspective.

To comprehend the present and chart an informed course for the future, it is essential to be aware of the past. Fifty years ago, William Dameshek introduced the conceptual construct of myeloproliferative disorders, a watershed event in the evolution of thought regarding that peculiar cluster of similar marrow conditions. The four major disorders that comprise the myeloproliferative group, polycythemia vera, chronic myeloid leukemia, myelofibrosis with myeloid metaplasia, and essential thrombocythemia, have interesting and instructive histories. This narrative review explores some of the most noteworthy episodes in those stories, from first descriptions to current understanding.

Chronic Disease↗
PubMed2003

Eureka moments.

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Attitude of Health Personnel↗