Review Article - Chronic Myeloid Leukemia: Cytogenetics and Molecular Genetics

Chronic myelogenous leukemia (CML) is a pleuripotent stem cell disorder characterized by proliferation and accumulation of mature myeloid cells and their progenitors. It is a first human malignancy where a specific marker- the Philadelphia (Ph) chromosome was linked to pathogenetic events of leukemogenesis. Around 99% of CML cases are Ph positive which include 91%-96% of cases with standard Ph resulting from a reciprocal translocation between long arm of chromosome 9 and 22 (Rowley, 1973) (Fig. 1); and 3%-8% of cases with variant or masked Ph (Rowley, et al. 1982; Kadam, et al. 1990; Bernstein, et al. 1984). Ph chromosome is also found in 5% of children and 15%-30% of adults with acute lymphoblastic leukemia (ALL) and around 2% - 6% of patients with acute myeloblastic leukemia (AML) (Kurzrock, et al. 1988; Specchia, et al. 1995; Kadam, et al. 1991) ). At gene level break occurs in ABL and BCR gene on chromosome 9 and 22 respectively, with the result the 22q11 -> qter segment including part of the BCR gene is translocated to ABL locus on chromosome 9 and reciprocally 3' segment of ABL gene is transposed and inserted to 5' segment of BCR gene on chromosome 22 (Fig. 2). The resulting BCR-ABL fusion on Ph chromosome is transcribed in to a chimerical RNA and then translated in to a fusion protein of varying size-p210, p190 (Fig. 2)

Investigation of recurrent deletion loci specific to conventional renal cell carcinoma by comparative allelotyping in major epithelial carcinomas

Objective: Loss of heterozygosity (LOH) studies were undertaken to investigate the consistently deleted loci/? tumor suppressor gene loci (TSG) on 3p in conventional renal cell carcinoma (cRCC). Materials and Methods: LOH studies were performed by polymerase chain reaction (PCR) using 15 micro satellite markers mapped in region 3p12-p26 on 40 paired cRCC tumors and normal kidney at Stages I-IV. Simultaneously, fluorescent in-situ hybridization (FISH) studies were performed to investigate the allelic deletion of fragile histidine triad (FHIT). Results: Our studies revealed three affected regions; 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 with differential frequencies in Group I (Stage I and II) and Group II (Stage III and IV). Incidence for D3S1234 (FHIT locus) and D3S2454 (3p13) was 75% and 83% in Group I and II, respectively. Comparative allelotyping in epithelial malignancies like lung, bladder, and breast tumors revealed LOH (frequency 14−20%) only in breast tumors for D3S2406, D3S1766 (distal to FHIT), and D3S1560 (distal to VHL, Von-Hippal Lindau). FISH using FHIT gene probe revealed deletions in cRCC (88%), breast (30%), and lung tumors (10%) with no deletions in bladder tumors and leukemias, signifying the importance of FHIT in the pathogenesis of tumors of epithelial origin. Conclusion: Our findings suggested FHIT deletion as an early and VHL deletion as an early and/or late event in cRCC. Additionally, studies also disclosed the recurrent deletions of flanking loci to FHIT and VHL in cRCC. The dilemma of interstitial or continuous deletion on 3p needs to be resolved by implementation of latest sensitive molecular techniques that would further help to narrow down search for TSG loci specific to cRCC, other than VHL and FHIT

Transient abnormal myelopoiesis: A case series and review of the literature

Transient abnormal myelopoiesis (TAM) is a rare and unique disorder affecting Down syndrome (DS) newborns. This case series presents 5 cases of Down syndrome with TAM diagnosed during 2007–2015 with detailed analysis of immunophenotypic data of each case. CD34, CD13, CD33, CD117, CD41, CD61, CD7 and HLA-DR are useful markers for characterization of blasts of TAM