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Reliability estimates for the Minimum Data Set for nursing home resident assessment and care screening (MDS).

The MDS is a core set of items, definitions, and response categories used to assess all of the nation's 1.5 million nursing home residents who reside in facilities participating in the Medicare or Medicaid programs. Further, the Health Care Financing Administration (HCFA) has proposed a rule that would require facilities to computerize MDS data and submit it to state and federal agencies, paving the way for a national database. This article describes the process of testing the reliability of the MDS items in 13 nursing homes in five states. The results demonstrate that MDS data gathered in a research effort attain reliabilities that make such data useful. MDS items met a standard for excellent reliability (i.e., intraclass correlation of .7 or higher) in key areas of functional status, such as cognition, ADLs, continence, and diagnoses. Sixty-three percent of the items achieved reliability coefficients of .6 or higher. Eighty-nine percent of the items in the MDS achieved .4 or higher.

Activities of Daily Living↗

Children with myelodysplastic syndrome (MDS) and increasing mixed chimaerism after allogeneic stem cell transplantation have a poor outcome which can be improved by pre-emptive immunotherapy.

We recently reported that virtually all children with acute leukaemia and myelodysplastic syndrome (MDS) who develop the phenotype of increasing mixed chimaerism (MC) after allogeneic stem cell transplantation (allo-SCT) will relapse. We therefore performed a prospective, multi-centre study focused on children with MDS (n = 65; advanced MDS = 44, refractory cytopenia = 21) after allo-SCT in order to determine to what extent relapse can be prevented by pre-emptive immunotherapy on the basis of increasing MC. Analyses of chimaerism in 44 patients with advanced MDS revealed 31 cases with complete chimaerism (CC)/low-level MC/transient MC, 11 cases with increasing MC and two cases with decreasing MC. The same analyses in 21 MDS patients with refractory cytopenia revealed 17 cases with CC/low-level MC, one case with increasing MC and three cases with decreasing MC. Pre-emptive immunotherapy performed on each patient that showed increasing MC improved event-free survival from 0%, as seen in prior studies, to 50%. We therefore conclude that pre-emptive immunotherapy is an effective treatment option to prevent impending relapse in children with MDS after allo-SCT.

Acute Disease↗

[Effect of shikonin and its derivatives, pentaacetylated shikonin (MDS-004) on granuloma formation and delayed-type allergy in experimental animals].

Of twelve reduced and acetylated derivatives of shikonin, a chemical constituent of Shikon, the accelerating activity on granuloma formation and the inhibitory activity on delayed-type allergy were investigated in order to find a compound having more characteristic effect than shikonin on wound healing in experimental animals. As a result, it was found that a reduced and pentaacetylated derivative of shikonin, MDS-004, has more excellent pharmacological activity. MDS-004 (0.1-1 mg/pellet) accelerated dose-dependently felt-pellet-induced granuloma formation when given topically together with felt-pellets in rats. It also produced strong inhibition against delayed-type allergies (ear edema) caused by oxazolone and dinitrofluorobenzene by topical application of up to 1 mg/ear to the ear skin of mice; its potency was far superior to that of shikonin. Orally administered MDS-004, unlike shikonin, inhibited carrageenan-induced hind paw edema, and exhibited tendency to heal acetic acid-induced gastric ulcer in rats. However, MDS-004, as well as commercial wound healing drugs tested and shikonin, did not show any healing action in the incised and open wound models in rats, if applied topically to the wound as 5 and 10% powders. On the other hand, MDS-004 did not produce irritative action on the ear skin at a topical dose of 1 mg/ear different from shikonin, and any behavioral changes after oral administration of 100 mg/kg in mice. These results suggest that a white powder MDS-004, different from deep purple shikonin, has accelerating action on granuloma formation without irritative action and stronger inhibitory action on delayed-type allergy by topical application than shikonin.

Animals↗

[Study on the origin of aberrant clones with chromosome abnormalities in MDS].

OBJECTIVE: To study the origin of aberrant clones with chromosome abnormalities in MDS. METHODS: Antibodies recognizing myeloid cells (CD33), B cells (CD19) and T cells (CD2) were used to sort bone marrow cells of ten MDS patients with chromosome abnormalities (trisomy 8 five cases, trisomy 8 accompanying trisomy 9 one case, trisomy 8 accompanying 7p- one case, 20q- two cases, t (1; 7) one case) by Immuno-Magnetic Bead technique, then the positive cells for CD33, CD19 or CD2 were detected respectively by interphase FISH using the centromeric probes for chromosomes 1, 7and 8, and the locus specific probe for 20q12. 200 to 300 cells were scored for each detection. RESULTS: FISH showed that trisomy 8, t (1; 7) and 20q- all affected CD33 positive cells, but not CD2 positive cells in these ten MDS patients. Only in one MDS patient, 20q- affected the CD19 positive cells. CONCLUSION: Our data suggest that the chromosomal aberrations in MDS are mostly restricted to myeloid cell lineages, but B lymphocytes are involved in minor MDS implying that abnormal clone originated from a multipotent hematopoietic progenitor.

Adult↗

[Effect of IL-15 on the proliferation, differentiation and anti-apoptosis of CD34+ cells in patients with MDS].

To study the effect of interleukin-15 (IL-15) on the proliferation, differentiation and apoptosis of MDS CD34(+) cells, CD34(+) cells of high enrichment were separated by MACS system, and cultured in liquid media with different concentration of IL-15 in treated group and without IL-15 in the control group. Apoptosis of hematopoietic precursors was assayed by propidium iodine staining and cell by FCM, and the other MDS CD34(+) cells were stained by cytochemical staining after culture. The results showed that after culture with IL-15 the proliferation and differentiation of MDS CD34(+) cells were obviously promoted. It was found the every lineage of mature cells developed, the expressions of cell surface antigens CD71, CD33 and CD19 all increased in the MDS CD34(+) cell treated with IL-15. It is suggested that IL-15 stimulates the proliferation and differentiation of MDS CD34(+) cells, and partly shows anti-apoptosis effects which may be applicable to the therapy MDS.

Antigens, CD↗

[Comparison of MDS-AC registration and conventional medical records in Iceland and other Nordic countries. A part of a Nordic study].

OBJECTIVE: Complex functional decline and comorbid state is an important indicator of outcome for hospital care of older adults. In today acute care it is important to quickly be able to target those who might benefit from geriatric assessment. The MDS-AC is an evaluation system for geriatric acute care patients that records functional impairment and co-morbid states. The object of this study was to compare the MDS-AC registration with the traditional nurses and doctors records for chosen variables important to older patient care in Iceland and other Nordic countries. METHODS: This was a randomised prospective Nordic study. The study took place in Reykjavík, Copenhagen, Umeå, Oslo and Helsinki. Participants in each country were chosen from 75 year old and older patients admitted to acute care medical wards, 160 patients from each country. The results presented here show data from selected variables collected with the MDS-AC instrument version 1,1 in the first 24 hours of admission, compared with hospital notes for the first 48 hours. RESULTS: For ADL and IADL impairments the medical record missed between 20 to 96% of items registered with the MDS-AC and between 33 to 100% when there is no impairment detected. This was true for all the participating Nordic countries but the Icelandic medical records were in comparison more often incomplete for the variables chosen. CONCLUSION: The MDS-AC documents better than traditional medical records several important variables relating to function among the elderly. It may be possible to improve documentation with a standardized instrument such as the MDS-AC.

Activities of Daily Living↗

In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients.

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.

Adult↗

Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS).

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid disorders characterized by morphologic dysplasia in one or more cell lineages. Dysplasia in MDS is associated with insufficient production of blood cells and consecutive cytopenia(s). The natural course and prognosis of MDS vary among patients and depend on genetic defects that occur during clonal evolution. In a significant group of patients (roughly 30%) progression to secondary leukemia is observed. These patients appear to have a grave prognosis. The treatment of patients with MDS has to be adjusted to the individual situation and age in each case. In many patients, control of blast cell production by palliative cytoreduction, continuous support with red blood cells, as well as other supportive measures, seem appropriate. In other patients, however, curative therapy (chemotherapy, stem cell transplantation) should be considered. The final decision to offer curative therapy must be based on many different factors including age and the overall situation of the patient. Recently established scoring systems aimed at predicting survival and evolution of leukemia in MDS may be helpful in this regard.

Adult↗

Programmed cell death is an intrinsic feature of MDS progenitors, predominantly found in the cluster-forming cells.

OBJECTIVE: Bone marrows (BM) of myelodysplastic syndrome (MDS) patients show increased proliferation and premature programmed cell death (PCD) in vivo as well as in vitro. We explored the proliferative capacity and apoptotic propensity of CD34+ progenitor cells of MDS patients excluding accessory cell interference. MATERIALS AND METHODS: CD34+/CD3-/CD19- cells of 5 MDS patients and 5 normal BM were sorted as single cells into single wells and were cultured in liquid medium. Wells were evaluated on days 4, 7, 10, and 14. PCD was determined by staining with annexin V-FITC. Growth rate and cell doubling time (Td) were calculated for each colony-forming cell. RESULTS: Normal BM CD34+ cells formed clusters and colonies and both showed increasing PCD in time, although within colonies the degree of apoptosis was twice as high (about 25%) as compared with clusters at all time points. In MDS increased cluster formation was observed at all evaluation points when compared to normal BM, whereas the number of colonies was markedly reduced (1/7 of normal). These colonies were also smaller, usually smaller than 100 cells. Significantly enhanced levels of PCD of clusters (53-79%) in combination with longer cell doubling times explain this slower formation of smaller colonies. Surprisingly, these colonies showed considerably lower levels of PCD (7-32%) as compared to normal (1-48%, median values). CONCLUSIONS: In the absence of stromal influences and accessory cells, this study in MDS patients showed intrinsically enhanced proliferation and apoptosis of cluster-forming cells, as the opposite was true for colony-forming cells.

Antigens, CD34↗

Predicting patient scores between the functional independence measure and the minimum data set: development and performance of a FIM-MDS "crosswalk".

OBJECTIVE: The functional status of rehabilitation patients is often measured using the Functional Independence Measure (FIM) in acute rehabilitation settings or the Minimum Data Set (MDS) in nursing homes. Because the relationship between the two instruments is unknown, preventing comparison of rehabilitation patients in different types of settings, a translation formula ("crosswalk") between items and subscales from the FIM and the MDS was developed and tested. DESIGN AND OUTCOME MEASURES: Using definitions recommended by an expert panel, MDS items were chosen and rescaled (termed "Pseudo-FIM(E)" items) to correspond to FIM items. The empiric relationships between Pseudo-FIM(E) and FIM scores were then measured using paired FIM-MDS assessments. SETTING AND PATIENTS: 173 rehabilitation patients admitted to six nursing homes. RESULTS: Pseudo-FIM(E) items could be defined for 12 of the 18 FIM items (8 motor and 4 cognitive items). Mean FIM and Pseudo-FIM(E) scores were not significantly different (p > .30) for 5 of the 12 items. Mean scores for the remaining 7 items and for motor and cognitive subscales were similar but statistically significantly different (p < .05). Intraclass correlation coefficients between the FIM and Pseudo-FIM(E) motor and cognitive subscales were both .81. CONCLUSIONS: FIM and MDS items can be used to predict item and subscale scores between the two instruments with reasonable accuracy. This capability will enhance efforts to compare case-mix between acute rehabilitation and nursing home rehabilitation patients, thus making feasible comparisons of the effectiveness (degree of improvement among similar patients) and efficiency (cost of care to obtain a given degree of improvement) of rehabilitation care in different types of settings.

Activities of Daily Living↗

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).

Adult↗

The MDS-CHESS scale: a new measure to predict mortality in institutionalized older people.

OBJECTIVES: To develop a scale predicting mortality and other adverse outcomes associated with frailty. DESIGN: Observational study based on Minimum Data Set (MDS) 2.0 and mortality data. SETTING: Ontario chronic hospitals. PARTICIPANTS: All chronic hospital patients (N = 28,495) assessed with the MDS 2.0 after mandatory implementation in July 1996 followed until May 1999. MEASUREMENTS: MDS 2.0 assessments done as part of normal practice mainly by registered nurses or multidisciplinary teams in a chronic hospital. Mortality data are available from the accompanying discharge tracking form. RESULTS: The MDS-Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score is a composite measure addressing changes in health, end-stage disease, and symptoms and signs of medical problems. It is a strong predictor of mortality (P <.0001) independent of the effects of age, sex, activities of daily living impairment, cognition, and do-not-resuscitate orders. It is also strongly associated with physician activity, complex medical procedures, and pain (P <.001 for each dependent variable). CONCLUSIONS: The CHESS score provides a useful new MDS-based test to predict mortality and to measure instability in health as a clinical outcome.

Activities of Daily Living↗

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Adolescent↗

Treatment strategies and issues in low/intermediate-1-risk myelodysplastic syndrome (MDS) patients.

Myelodysplastic syndromes (MDS) are a heterogeneous group of progressive bone marrow neoplastic disorders associated with increased risk for transformation to acute leukemia. Hallmarks of MDS are peripheral blood cytopenias (especially anemia), frequently with hypercellular bone marrow, and dysplastic changes in one or more hematopoietic lineages. The wide variation in clinical presentation has confounded treatment strategies and hindered the development of new therapies. However, improved classification and prognostic systems are providing a more refined stratification of patients, helping to guide treatment and management decisions as well as to appropriately select patients for clinical trials. Patients with International Prognostic Scoring System classifications of low- and intermediate-1 (Low/Int-1) risk are considered to have "low-risk" MDS. These patients are primarily treated with low-intensity supportive care, especially red blood cell transfusions, to treat their symptoms and maintain their quality of life. In small subsets of Low/Int-1-risk patients with MDS, hematopoietic cytokines or antithymocyte globulin may reduce transfusion requirements. The drawbacks to these treatments are high failure rates, even with improved predictive models, and the high cost of cytokines. Regardless of risk category, a patient's age and existing comorbidities must be factored into treatment decisions. It is anticipated that trials with new and investigational agents may soon provide definitive treatments for patients with Low/Int-1-risk MDS when used alone or in conjunction with supportive measures.

Antilymphocyte Serum↗

MetaCCI: meta cell-cell interaction inference and its application to CCIs characteristics of MDS.

MOTIVATION: Cell-cell interactions (CCIs) are fundamental to multicellular organisms and play crucial roles in diverse biological processes and disease mechanisms. Understanding CCIs is vital for deciphering disease pathogenesis and developing therapeutic strategies. Although numerous computational methods have been developed to infer CCIs from complex biological data, most existing approaches rely primarily on single-gene expression levels and ligand-receptor databases, often failing to capture the nuanced network-wide changes characteristic of disease states. RESULT: We propose MetaCCI, a novel computational strategy that integrates meta-information into CCI inference by extending the traditional gene expression-based analysis to a gene regulatory network framework. MetaCCI meticulously combines established ligand-receptor pairs with quantitative insights into gene behavior within complex gene networks, enabling the precise extraction of relevant targets for CCI inference. Subsequently, CCI inference was performed using an eigen cell co-expression network, providing a more holistic view of cell-cell communication. Monte Carlo simulations demonstrated that MetaCCI consistently outperforms existing methods in CCI inference. We applied MetaCCI to characterize cell-cell communication in Myelodysplastic Syndromes (MDS). Our results identified distinct interaction patterns in MDS compared with normal cell populations, specifically highlighting the loss of CCIs between "Dendritic cells and Hematopoietic precursor cells" and between "Dendritic cells and Hematopoietic multipotent progenitor cells" as characteristic features of MDS. Furthermore, FABP5, CD63, and HMGB1 were identified as MDS-specific markers. These findings suggest that diminished CCIs involving dendritic cells, hematopoietic precursor cells, and multipotent progenitor cells are pivotal to MDS pathogenesis. AVAILABILITY AND IMPLEMENTATION: The MetaCCI software is freely available at https://github.com/HeewonGitHub/MetaCCI. An archived version of the software and example datasets used in this study is available at Zenodo: https://doi.org/10.5281/zenodo.20101527.

Myelodysplastic Syndromes↗

Matrix metalloproteinase inhibitor reduces apoptosis induction of bone marrow cells in MDS-RA.

BACKGROUND AND OBJECTIVES: We examined the involvement of apoptosis with myelodysplastic syndrome (MDS) accompanied by peripheral cytopenias despite normo-hypercellular bone marrow. MATERIALS AND METHODS: Bone marrow smears from 31 patients with MDS-refractory anemia (RA) and five normal controls were stained using the in situ end labeling (ISEL) method. Next, the inhibitory effects of a caspase-3 inhibitor, matrix metalloproteinase inhibitor (MMPI), anti-tumor necrosis factor (TNF)-alpha or anti-Fas antibody upon the apoptosis induction in overnight cultures of bone marrow cells from the patients were examined. Further, TNF-alpha, transforming growth factor (TGF)-beta and soluble Fas ligand (sFasL) concentrations in culture supernatants of the cells were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The incidence of ISEL-positive cells among MDS patients was significantly higher than in normal controls (50.8 +/- 14.0% vs. 11.3 +/- 2.4%; P < 0.0001). A caspase-3 inhibitor reduced significantly the ISEL-positive rates (32.6 +/- 15.2% vs. 50.2 +/- 16.5%; P < 0.0001). Anti-TNF-alpha or anti-Fas antibody reduced the ISEL-positive rates significantly (28.2 +/- 6.0%, 29.2 +/- 5.8%, vs. 44.2 +/- 3.4%, P < 0.001, P = 0.001, respectively). KB-R7785 also significantly decreased the ISEL-positive rates (18.0 +/- 9.3% vs. 43.6 +/- 14.0%; P < 0.0001). The concentration of TNF-alpha was significantly reduced by KB-R7785 (P < 0.05), whereas that of TGF-beta was not. Concentration of sFasL was under detectable level in the present assay system. The derivatives of KB-R7785 that can be administrated orally showed inhibitory effect on apoptosis induction as well. CONCLUSIONS: These findings suggest that MMPIs inhibits the apoptosis induction of MDS bone marrow cells via the inhibition of TNF-alpha and probably sFasL secretion, and that MMPIs can be used to control the abnormal induction of apoptosis in MDS.

Adult↗

MDS coordinator relationships and nursing home care processes.

This study describes how Minimum Data Set (MDS) coordinators' relationship patterns influence nursing home care processes. MDS coordinators interact with nursing home staff to coordinate resident assessment and care planning, but little is known about how they enact this role or influence particular care processes beyond paper compliance. Guided by complexity science and using two nursing home case studies, the authors describe MDS coordinators' relationship patterns by assessing the extent to which they used and fostered good connections, new information flow, and cognitive diversity. MDS coordinators at one site fostered new information flow, good connections, and cognitive diversity, which positively influenced assessment and care planning, whereas those at the other site did little to foster these three relationship parameters, with little influence on care processes. This study revealed that MDS coordinators are an important new source of capacity for the nursing home industry to improve quality of care.

Aged↗

Molecular Pathogenesis of MDS.

Clonal disorders of hematopoiesis, such as myelodysplastic syndromes (MDS) and myeloproliferative diseases (MPD), affect both hematopoietic stem cells and progenitor cells within the erythroid, platelet and granulocytic lineages and can have devastating consequences in children and adults. The genetic features of these diseases often include clonal, nonrandom chromosomal deletions (e.g., 7q-, 5q-, 20q-, 6q-, 11q- and 13q-) that appear to inactivate tumor suppressor genes required for the normal development of myeloid cells (reviewed in Bench and Fenaux). These putative tumor suppressors have proved to be much more difficult to identify than oncogenes activated by chromosomal translocations, the other major class of chromosomal lesions in MDS and MPD. Although MDS and MPD are almost certainly caused by mutations in stem/progenitor cells, the role of inactivated tumor suppressor genes in this process remains poorly understood. In a small portion of myeloid diseases, mutations have been identified in genes encoding factors known to be required for normal hematopoiesis, such as PU.1, RUNX1, CTNNA1 (alpha-catenin) and c/EBPalpha, and implicating these genes as tumor suppressors. Nonetheless, the identities of most deletion-associated tumor suppressors in these diseases remains elusive, despite complete sequencing of the human genome. The deleted regions detected by cytogenetic methods are generally very large, containing many hundreds of genes, thus making it hard to locate the critical affected gene or genes. It is also unclear whether dysfunctional myelopoiesis results from haploinsufficiency, associated with the deletion of one allele, or from homozygous inactivation due to additional point mutations or microdeletions of the retained wild-type allele. In general MDS have proved surprisingly resistant to conventional treatments. Targeted therapeutic advances in MDS will likely depend on a full comprehension of underlying molecular mechanisms, in particular the tumor suppressor genes lost through clonal, nonrandom chromosomal deletions, such as the 7q- and (del)5q.

Adult↗