Acute Leukemias with No Specific Cytogenetic Findings

A substantial number of cases of AML will not have any of the specific genetic abnormalities. Cases of AML with no defining abnormalities are designated acute myeloid leukemia, NOS. In such cases, the following diagnostic categories -defined entirely by morphological criteria - may be used. Acute monoblastic and monocytic leukemia Acute panmyelosis with myelofibrosis Testing to establish the absence of any of the specific cytogenetic abnormalities is essential when these diagnostic categories...

DNA Sequencing

Sequencing refers to a set of analytical methods to determine the sequence or the order of nucleotide bases (adenine, guanine, cytosine, thymine) within a DNA molecule. In 1977, two independent research groups published ground-breaking technological developments that facilitated the ability to determine the sequence of DNA. In brief, Maxam and Gilbert 66 used chemicals to fragment radiolabeled DNA at specific bases, while Sanger and colleagues 67 used radiolabeled chain-terminating inhibitors....

References

Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France International Agency for Research on Cancer 2008. 2. Merrick TA Beavis KG, Bhagat G, et al. GP17-A2, Clinical laboratory safety approved guideline - second edition. Clin Lab Stand Inst.2004 24 1-92. 3. Sewell DL Callihan DR, Denys GA, et al. RE. M29-A, Protection of laboratory workers from occupationally acquired infections approved guideline - second edition. Clin...

Info

Fig. 1.3 Schematic of immunoglobulin heavy chain (IGH) receptor gene. Basic process of somatic recombination at the IGH locus occurring within developing B cells. Random selection and rearrangement of first diversity (Dh) and joining (Jh) gene segments, followed next by a variable (Vh) gene segment completes the primary V-D-J coding sequence. Antigen diversity is derived from the unique nucleotide sequences of the randomly selected gene segments. Further diversity stems from terminal...

Plasma Cell Myeloma

Identification of recurrent chromosomal abnormalities by conventional analysis in plasma cell myeloma (PCM) has been hindered by patchy bone marrow infiltration, low mitotic index of malignant plasma cells in vitro, the poor quality of metaphase chromosomes, and the cryptic nature of some IgH gene rearrangements observed in this disease. An abnormal karyotype is found in 30-40 of cases, more often in advanced stages than in newly diagnosed patients. Highly complex karyotypes are also common,...

Clinical Indications for FISH Testing in Hematolymphoid Disorders

Common indications for FISH testing in hematolymphoid malignancies include the following (1) confirmation of chromosomal abnormalities detected by conventional cytogenetics and establishment of FISH signal pattern for follow-up study, (2) detection of chromosomal abnormalities when clinical and morphologic findings are suggestive of a specific chromosomal abnormality e.g., t(11 14) in mantle cell lymphoma , (3) characterization of genetic aberrations using a panel of disease-specific FISH...

Altered Notch Signaling in TALL

NOTCH1 encodes a heterodimeric receptor that critically regulates cell fate decisions by multipotent progenitors during development. As such, NOTCH1 plays an important role in regulating proliferation, apoptosis, and differentiation in these cells. Within the hematopoietic system, NOTCH1 critically influences the generation of T-cells at multiple steps in their ontogeny 87, 88 . The commitment of hematopoietic progenitors to the T-cell lineage is dependent on NOTCH1 signaling. Loss of NOTCH1...

BCL6 Alterations in DLBCL

The B-cell CLL lymphoma 6 (BCL6) gene, located on chromosome 3q27, encodes a zinc finger protein that is a transcriptional repressor normally expressed in germinal Table 6.4 Genetic alterations in other lymphomas of large B cells Primary mediastinal (thymic) +9p24, +2p15, lymphoma DLBCL associated with chronic inflammation Lymphomatoid Large B-cell lymphoma arising in HHV-8-associated multicentric Castleman disease Primary effusion lymphoma t(2 17) (CLTC-ALK) t(2 5)less common None Similar to...

Molecular Pathology of Mature BCell and TCell Lymphomas

Bahler, and Marsha C. Kinney Keywords B-cell maturation Immunoglobulin heavy chain (IgH) gene rearrangement Kappa immunoglobulin light chain gene rearrangement Lambda immunoglobulin light chain gene rearrangement Class (isotype) switch Somatic hypermutation Clonality testing B-cell Follicular lymphoma B-cell lymphoma CLL 2 (BCL2) translocation -t(14 18) Mantle cell lymphoma Cyclin D1 translocation -t(11 14) Diffuse large B-cell lymphoma (DLBCL) Germinal center type...