Suspected (e.g., persistent unexplained cytopenia, circulating peripheral blasts etc.) MDS or MDS/MPN overlap disorders and undergoing diagnostic work-up with planned bone marrow assessments OR

Diagnosed with de novo or therapy-related MDS within 12-months of enrollment per the World Health Organization (WHO) criteria and undergoing clinical evaluation and planned bone marrow assessments to confirm MDS or to evaluate disease status

Bone marrow aspirate expected to be performed within 1 week of registration, and in all cases must be performed no later than 4 weeks after enrollment

Age 18 or older

No prior treatment for MDS at entry and through the time of the entry bone marrow aspirate

No treatment with hematopoietic growth factors in prior 6 months

If anemic without prior MDS diagnosis, the following tests within the prior 6 months; values that are significantly outside of normal range do not exclude participation but should prompt investigation of alternative etiologies for anemia
* B12 level 
* Serum folate
* Mean corpuscular volume (MCV)
* Red cell distribution width (RDW)
* Ferritin
* Iron studies (iron, total iron-binding capacity [TIBC] test, percent saturation)

No diagnosis of a solid tumor or hematologic malignancy within two years prior to enrollment except for in situ cancer of the skin (basal or squamous cell), cervix, bladder, breast, or prostate

No treatment with radiation therapy in the two years prior to registration

No non-hormonal treatment for malignancy within the two years prior to registration

No established hereditary bone marrow failure syndrome

No known primary diagnosis of aplastic anemia, classical paroxysmal nocturnal hemoglobinuria, amegakaryocytic thrombocytopenic purpura, or large granular lymphocyte leukemia

Not enrolled in the Connect MDS/Acute Myeloid Leukemia (AML) Disease Registry

In participants with suspected MDS and prior to registration with subsequent bone marrow evaluation, alternative causes for the cytopenias should be considered (e.g., internal bleeding, autoimmune cytopenias, thyroid disorders, other causes of anemia etc.); in select individuals, the following tests could be performed to assist in the diagnostic work-up; these evaluations are not required by the protocol; however, abnormal results in advance of enrollment may reduce the number of non-MDS cases
* Copper, serum level
* Direct antiglobulin test
* Antinuclear antibody (ANA) test
* Creatinine
* Calculated glomerular filtration rate (GFR)
* Thyroid-stimulating hormone (TSH) tests performed in prior 6 months
** Based on centralized pathology review, participants will be classified into the longitudinal cohort of cases (MDS; MDS/MPN overlap disorders; AML with < 30% blasts without core binding factor or acute promyelocytic leukemia [AML < 30% blasts including chromosomal rearrangements between chromosomes 8 and 21 and within chromosome 16 as well as t(15;17)]; idiopathic cytopenia of undetermined significance [ICUS], or at risk based on selected genetic markers) and the cross-sectional cohort (all others); it is not known in advance what percentages of individuals will fall into each cohort; in addition to baseline biological samples, longitudinal samples and data will be collected for approximately 2000 cases of MDS or MDS/MPN overlap disorders and 500 cases of ICUS assigned to the longitudinal cohort; sample and data collection will cease at baseline for all cases assigned to the cross-sectional cohort; submitted samples will be reviewed by a central pathologist to determine eligibility for the longitudinal cohort (i.e., an MDS, MDS/MPN, AML with < 30% blasts without core binding factor or acute promyelocytic leukemia, or ICUS diagnosis); should a discrepancy in diagnosis occur between the central review and study site, the study site will be notified to allow for additional information to be submitted to clarify the diagnosis; such notifications will not occur in real time, and are not intended to assist in patient care; additional central sequencing of selected genetic targets will be performed

PRIMARY OBJECTIVES:
I. To develop a high-quality clinical database containing clinical history, including environmental exposure history, presenting signs and symptoms, diagnostic testing results, co-existing diseases, therapies and response to therapies, disease progression, quality of life and survival.
II. To develop a high-quality biorepository linked to the clinical data that will facilitate diverse studies, including genetic, epigenetic, immunologic, proteomic, and cell-functional and cell-phenotypic studies through the development of: central communication with the biorepository to ensure timely and accurate collections and biospecimen data appended to the clinical database; defined standard operating procedures for the collection, processing, storage and distribution, with special emphasis on processing protocols fit-for-purpose to sample requirements for downstream testing; and quality management procedures to ensure minimal numbers of errors in the management of the biospecimens.
III. To facilitate broad use of these linked data and specimens to support studies focused on: improving diagnostic accuracy, risk-stratification and prognostication, and medical decision-making in MDS; understanding quality of life and its relationship to changing disease and treatment status; understanding the pathogenesis of MDS and diverse MDS subtypes, including genetic, epigenetic, immunologic mechanisms; optimizing treatment strategies for specific subtypes of MDS; identifying novel biomarkers for MDS outcomes; and identifying novel targets for therapeutic interventions in MDS.

SECONDARY OBJECTIVES:
I. Detecting improved prognostic factors in low risk MDS. (Potential Studies)
II. Detecting markers of improved response to hypomethylating therapy. (Potential Studies)
III. Quality of life (QOL) and anemia therapy. (Potential Studies)
IV. Genetic factors in patients with complex karyotype. (Potential Studies)
V. Prognostic significance of splicing factor 3b subunit 1 (SF3B1) in MDS patients with refractory anemia with ring sideroblasts (RARS). (Potential Studies)

OUTLINE:
Patients undergo blood, bone marrow, eyebrow hairs, and buccal swab. Patients' medical records, baseline laboratory tests, quality of life, and diagnostic information including pathology reports and treatment history are also reviewed.

After the baseline visit, patients are followed up every 6 months. Follow up visits include disease evaluation, physical examination and collection of peripheral blood sample. Bone marrow biopsy and aspiration is performed when clinically necessary. Patients also complete the MDS-specific Qualify of Life in Myelodysplasia Scale (QUALMS), Functional Assessment of Cancer Therapy-General (FACT-G) (version 4), the Patient Reported Outcome Measurement Information System (PROMIS) Short Form version 1.0-Fatigue 7a, and the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L).