Inherited Bone Marrow Failure and Chromosome Instability Syndromes and their Cancer Predisposition

Inherited bone marrow failure syndromes (IBMFS) and chromosome instability syndromes (CIS) are the most classic and representative genetic syndromes. They are classified as genetic rare diseases, typically with complex medical complications in the delay of mental and physical development. Commonly, these syndromes present with different degrees of dysmorphics; organs/systems dysfunction generally and these syndromes have higher risk of inherited solid cancer and leukemia predisposition due to the similar pathway of DNA defects. These syndromes are often hard to diagnose and they overlap with their phenotypes clinically. Very importantly cancers from the germ line mutation of these syndromes require different treatment strategies with the sporadic malignancies. The significance of recognition of such diseases is not only beneficial to patients phenotypically affected but also to individuals phenotypically unaffected and members/relatives of the family. Remarkable advances have been made in the definition and classification of these genetic syndromes. Identification of the IBMFS and CIS has led to important advances in the understanding of the genotypes, guiding the clinical practice of the phenotypes. Interestingly, such studies provided insights into the function of the various DNA repair pathways. Fanconi anemia studies are an example in IBMFS and CIS is named as the paradigm of the studies of cancer and aging

Milestone Histories and Paradigmatic Genetic Discoveries of Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is classified as a hematological malignant rare disease by National Organization for Rare Disease (NORD, USA) based on the estimated incidence of 1–2 cases/100,000 per year internationally. CML occurs in all ages but commonly seen in the 45–55 years group. Males are slightly more affected than females. CML is one of the oldest known diseases with new faces and one of the fastest developing diseases with many extraordinary discoveries in human history of conquering the disease. CML possesses at least Nine First findings in leukemia and cancer research and even in human medical histories: the First named as leukemia in 1845, the First of a live case of CML patient diagnosed in 1846, the First used of arsenic in CML treatment in 1865, the First defined as a myeloproliferative disorder in 1951, the First finding of Philadelphia chromosome (Ph chromosome) in 1960, the First finding of chromosome 9 and 22 translocations in 1973, the First identified as a clonal hematological malignancy derived from the stage of pluripotent bone hematopoietic stem cells in 1977, the First finding of the chromosomal fusion gene-BCR-ABL as an oncogene in 1984, and the First designed target therapy of use of tyrosine kinase inhibitor (TKI) in 1998. The footprints of the studies on CML established the milestone histories. Remarkable and fascinating genetic discoveries were made of the mysteries of human diseases, the multiway translocation of Ph chromosome, and the latest issues. The association of the combination of chronic myeloid leukemia and chronic lymphocytic leukemia will be reviewed in this chapter with the aim of increasing the understanding of CML further from laboratory bench to clinical bedside

On defining partition entropy by inequalities

Partition entropy is the numerical metric of uncertainty within a partition of a finite set, while conditional entropy measures the degree of difficulty in predicting a decision partition when a condition partition is provided. Since two direct methods exist for defining conditional entropy based on its partition entropy, the inequality postulates of monotonicity, which conditional entropy satisfies, are actually additional constraints on its entropy. Thus, in this paper partition entropy is defined as a function of probability distribution, satisfying all the inequalities of not only partition entropy itself but also its conditional counterpart. These inequality postulates formalize the intuitive understandings of uncertainty contained in partitions of finite sets.We study the relationships between these inequalities, and reduce the redundancies among them. According to two different definitions of conditional entropy from its partition entropy, the convenient and unified checking conditions for any partition entropy are presented, respectively. These properties generalize and illuminate the common nature of all partition entropies