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Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome.

Zhou T, Chen P, Gu J, Bishop AJ, Scott LM, Hasty P, Rebel VI - Int J Mol Sci (2015)

Bottom Line: Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves.Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions.It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations.

View Article: PubMed Central - PubMed

Affiliation: Greehey Children's Cancer Research Center, University of Texas Health Science Center San Antonio (UTHSCSA), 8403 Floyd Curl Drive, San Antonio, TX 78229, USA. zhoubaipi@gmail.com.

ABSTRACT
Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

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Related in: MedlinePlus

Characteristic features of myelodysplastic syndrome (MDS) in humans. MDS is thought to originate from a mutated Hematopoietic stem cell (HSC). Approximately 30% of MDS patients progress to AML (acute myeloid leukemia) [30]. With each stage, an increased number of mutations in essential genes can be observed [24,31]; the classic representation of both diseases is depicted. Although MDS and AML have very similar clinical symptoms, they can be distinguished from each other by cell counts in the peripheral blood and pathological review of the bone marrow. Classical MDS is associated with myelodysplasia in the bone marrow and cytopenia in one or more myeloid lineages in the peripheral blood. However, a level of >20% myeloblasts in the bone marrow is indicative for AML and excludes the diagnosis of MDS [39,40]. Signs of myelodysplasia can still be present in bone marrow samples of MDS patients that have progressed to AML. In some patients, myelodysplasia and <20% myeloblasts in the bone marrow is accompanied with cytosis in one of the peripheral blood lineages; these patients are diagnosed with MDS/MPN (myleoproliferative neoplasm) overlap disease, which is a different disease altogether [41]. MDS-IC, MDS initiating cell; AML-IC, AML initiating cell; * Cytopenia, significantly fewer cells than normal in one of the peripheral blood lineages; ¶ Leukocytosis, significantly more leukocytes than normal in the peripheral blood; † Myelodysplasia, abnormal blood cell morphology.
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ijms-16-00966-f001: Characteristic features of myelodysplastic syndrome (MDS) in humans. MDS is thought to originate from a mutated Hematopoietic stem cell (HSC). Approximately 30% of MDS patients progress to AML (acute myeloid leukemia) [30]. With each stage, an increased number of mutations in essential genes can be observed [24,31]; the classic representation of both diseases is depicted. Although MDS and AML have very similar clinical symptoms, they can be distinguished from each other by cell counts in the peripheral blood and pathological review of the bone marrow. Classical MDS is associated with myelodysplasia in the bone marrow and cytopenia in one or more myeloid lineages in the peripheral blood. However, a level of >20% myeloblasts in the bone marrow is indicative for AML and excludes the diagnosis of MDS [39,40]. Signs of myelodysplasia can still be present in bone marrow samples of MDS patients that have progressed to AML. In some patients, myelodysplasia and <20% myeloblasts in the bone marrow is accompanied with cytosis in one of the peripheral blood lineages; these patients are diagnosed with MDS/MPN (myleoproliferative neoplasm) overlap disease, which is a different disease altogether [41]. MDS-IC, MDS initiating cell; AML-IC, AML initiating cell; * Cytopenia, significantly fewer cells than normal in one of the peripheral blood lineages; ¶ Leukocytosis, significantly more leukocytes than normal in the peripheral blood; † Myelodysplasia, abnormal blood cell morphology.

Mentions: MDS patients present with signs of a degenerating hematopoietic tissue: chronic fatigue (due to a lack of functional red cells), unexplainable bleedings and bruises (lack of platelets) and/or recurrent infections (lack of leukocytes). MDS is furthermore characterized by genomic instability and a high propensity to progress into acute myeloid leukemia (AML (acute myeloid leukemia); Figure 1) [30].


Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome.

Zhou T, Chen P, Gu J, Bishop AJ, Scott LM, Hasty P, Rebel VI - Int J Mol Sci (2015)

Characteristic features of myelodysplastic syndrome (MDS) in humans. MDS is thought to originate from a mutated Hematopoietic stem cell (HSC). Approximately 30% of MDS patients progress to AML (acute myeloid leukemia) [30]. With each stage, an increased number of mutations in essential genes can be observed [24,31]; the classic representation of both diseases is depicted. Although MDS and AML have very similar clinical symptoms, they can be distinguished from each other by cell counts in the peripheral blood and pathological review of the bone marrow. Classical MDS is associated with myelodysplasia in the bone marrow and cytopenia in one or more myeloid lineages in the peripheral blood. However, a level of >20% myeloblasts in the bone marrow is indicative for AML and excludes the diagnosis of MDS [39,40]. Signs of myelodysplasia can still be present in bone marrow samples of MDS patients that have progressed to AML. In some patients, myelodysplasia and <20% myeloblasts in the bone marrow is accompanied with cytosis in one of the peripheral blood lineages; these patients are diagnosed with MDS/MPN (myleoproliferative neoplasm) overlap disease, which is a different disease altogether [41]. MDS-IC, MDS initiating cell; AML-IC, AML initiating cell; * Cytopenia, significantly fewer cells than normal in one of the peripheral blood lineages; ¶ Leukocytosis, significantly more leukocytes than normal in the peripheral blood; † Myelodysplasia, abnormal blood cell morphology.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4307285&req=5

ijms-16-00966-f001: Characteristic features of myelodysplastic syndrome (MDS) in humans. MDS is thought to originate from a mutated Hematopoietic stem cell (HSC). Approximately 30% of MDS patients progress to AML (acute myeloid leukemia) [30]. With each stage, an increased number of mutations in essential genes can be observed [24,31]; the classic representation of both diseases is depicted. Although MDS and AML have very similar clinical symptoms, they can be distinguished from each other by cell counts in the peripheral blood and pathological review of the bone marrow. Classical MDS is associated with myelodysplasia in the bone marrow and cytopenia in one or more myeloid lineages in the peripheral blood. However, a level of >20% myeloblasts in the bone marrow is indicative for AML and excludes the diagnosis of MDS [39,40]. Signs of myelodysplasia can still be present in bone marrow samples of MDS patients that have progressed to AML. In some patients, myelodysplasia and <20% myeloblasts in the bone marrow is accompanied with cytosis in one of the peripheral blood lineages; these patients are diagnosed with MDS/MPN (myleoproliferative neoplasm) overlap disease, which is a different disease altogether [41]. MDS-IC, MDS initiating cell; AML-IC, AML initiating cell; * Cytopenia, significantly fewer cells than normal in one of the peripheral blood lineages; ¶ Leukocytosis, significantly more leukocytes than normal in the peripheral blood; † Myelodysplasia, abnormal blood cell morphology.
Mentions: MDS patients present with signs of a degenerating hematopoietic tissue: chronic fatigue (due to a lack of functional red cells), unexplainable bleedings and bruises (lack of platelets) and/or recurrent infections (lack of leukocytes). MDS is furthermore characterized by genomic instability and a high propensity to progress into acute myeloid leukemia (AML (acute myeloid leukemia); Figure 1) [30].

Bottom Line: Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves.Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions.It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations.

View Article: PubMed Central - PubMed

Affiliation: Greehey Children's Cancer Research Center, University of Texas Health Science Center San Antonio (UTHSCSA), 8403 Floyd Curl Drive, San Antonio, TX 78229, USA. zhoubaipi@gmail.com.

ABSTRACT
Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

Show MeSH
Related in: MedlinePlus