Genome abnormalities Most studies on the genomic abnormalities in<unk>  did not distinguish between the disorder's phenotypes. However, familial studies have found that hereditary factors can contributor to the development of specifically CLL/SLL MLB. Of all the hematologic malignancies, CLL/SLL is the most likely to afflict multiple family members with estimates of familial CLL/SLL ranging from 6 to 10% of all CLL/SLL cases. About 18% of first-degree relatives of individuals with familial CLL/SLL and ~16% of the close relatives of patients with non-hereditary CLL/SLL have CLL/SLL<unk> . These associations strongly suggest that inheritable genomic abnormalities contribute to the development of CLL/SLL MLB and, possibly, the progression of this disorder to CLL/SLL. Chromosome abnormalities, single nucleotide polymorphisms (SNPs, i.e. substitutions of a single nucleotide in a DNA sequence at a specific position in the genome) and gene mutations, while each occurs in <15% of cases, are present in CLL/SLL<unk>  and to some extent are similar to those found in CLL/SLL. For example, position 21.33 to 22.2 on the long (i.e. "q" ) arm of chromosome 13 is a potential susceptibility locus for familial CLL/SLL. This locus has been identified not only in individuals with familial CLL/SLL but also in their blood relatives who have CLL/SLL<unk> . More than 20 SNPs are confirmed risk factors for the development of CLL/SLL; at least 6 of these are also risk factors for CLL/SLL<unk> . Finally, the following studies were done on individuals defined as having<unk>  but din not give its phenotype. Here, these patients are presumed to have the CLL/SLL<unk>  phenotype. Individuals with low-count and high-count<unk>  shared with CLL/SLL patients many genomic abnormalities including: deletions of the long arm (i.e. "q" arm) of chromosomes 11 and 13; deletion of the short arm (i.e. "p" arm) of chromosome 17; trisomy of chromosome 12; and mutations in NOTCH1, BIRC3, SF3B1, MYD88, ATM, and TP53 genes. In general, the presence and frequency of the mutations in high count<unk>  were closer than the low count MLB in resembling those in CLL/SLL. All three groups had mutations in the IGH@ region of chromosome 14. This region contains the complex gene that encodes the VDJ region of the heavy chain component of antibodies. Among these mutations, IVGH4-59/61 is most often mutated in low-count<unk>  while IGHV1-69, IGH2-5, IGHV3-23, IGH23-33, IGHV3-48, and IGHV4-34 are most often mutated in high-count<unk>  and CLL/SLL. Finally, genetic abnormalities such as the deletion of the q arm in chromosome 13 found in low count<unk>  are more commonly associated with a favorable prognosis in CLL/SLL while those found in high count<unk> , e.g. deletions in the q arm of chromosome 11 or p arm of chromosome 17 are commonly associated with unfavorable prognoses in CLL/SLL. Individuals with<unk> -MZ have<unk>  B cell cells that bear complex and distinctive genomic abnormalities, such as deletions and translocations involving chromosome 7, presence of an isochromosome 17, and, rarely, mutations in the NOTCH2 and KLF2 genes. Some of these genomic abnormalities are similar to those found in splenic marginal zone lymphomas and some of the<unk> -MZ patients that bore these abnormalities developed this lymphoma. The genetic abnormalities in atypical and non-CLL/SLL<unk>  have not been well-defined. The cited studies suggest that there is a step-wise accumulation of genomic abnormalities that lead to CLL/SLL<unk>  and<unk> -MZ and then to overt malignancy. It presumed that similar accumulations led to the development of atypical and non-Cll/SLL MLB and than to their respective malignancies. However, given the number and diversity of these abnormalities, it is unclear which are critical determinants of these disorders. A recent model based on laboratory studies of normal CD19+ B cell,<unk>  CLL/SLL<unk>  cells, and CLL/SLL malignant cells found that their accumulation of genomic abnormalities may be caused by progressively increasing: 1) double strand breaks in DNA, 2) activation of non-homologous end joining error-prone DNA repair mechanisms, and 3) consequential accumulation of genomic abnormalities which promote the clonal development, survival, proliferation, and ultimately malignancy of the involved B cells. Infectious diseases Studies have identified<unk>  in ~30% of patients infected with the hepatitis C virus, found increased risks of CLL/SLL-MLB in patients with pneumonia, and decreased risk of CLL/CSS<unk>  in patients who have been vaccinated for influenza or pneumonia. Herpes Zoster and various upper respiratory tract infections are also considered to be risk factors for developing CLL/SLL<unk> . It seems possible that the pathogens involved in these diseases provide antigens that stimulate the development of<unk>  although further studies are required to explore this hypothesis further. Blood transfusion One study diagnosed<unk>  in 0.14% of blood donors and suggested a possibility that<unk>  is transmitted through blood transfusions. This concern as well as the concern of transmitting CLL/SLL in transfusions of blood from patients with CLL/SLL has been voiced elsewhere. However, a study conducted in Sweden and Denmark on 7,413 recipients of blood from 796 donors diagnosed with CLL/SLL found no evidence of CLL/SLL clustering among recipients of blood from these donors. It therefore appears that CLL/SLL and, by implication, CLL/SLL<unk>  have little or no ability to be transmitted by blood transfusions, at least when the donors and recipients are unrelated. Bone marrow transplantation Rare cases of<unk>  have been reported to develop in individuals who receive a, autologous stem cell bone marrow transplant from donors who have<unk> . Currently, the risk of this development is unclear and requires further study. In those special cases where related donors are used for transplantation, it may be useful to screen these donors for<unk> .
Monoclonal B-cell lymphocytosis
Persistent polyclonal B-cell lymphocytosis
Abscess of thymus
Idiopathic CD4+ lymphocytopenia
Cutaneous lymphoid hyperplasia
Persistent generalized lymphadenopathy
Thymic hypoplasia
Lymphoid neoplasms with plasmablastic differentiation