PMID- 11750052
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20190816
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 131
IP  - 2
DP  - 2001 Dec
TI  - Fluorescence in situ hybridization: a highly efficient technique of molecular 
      diagnosis and predication for disease course in patients with myeloid leukemias.
PG  - 125-34
AB  - The accuracy of cytogenetic diagnosis in the management of hematological 
      malignancies has improved significantly over the past 10 years. Fluorescence in 
      situ hybridization (FISH), a technique of molecular cytogenetics, has played a 
      pivotal role in the detection of unique sub-microscopic chromosomal 
      rearrangements that helped in the identification of chromosomal loci, which 
      contain genes involved in leukemogenesis. We studied the feasibility and 
      sensitivity of the FISH technique for molecular analysis of translocations 
      markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring 
      the disease in 21 patients with chronic myeloid leukemia (CML) who received 
      interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation 
      (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who 
      received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied 
      conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at 
      diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had 
      t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) 
      (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL 
      fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat 
      follow-up FISH studies could be done in two cases in remission, which 
      demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status 
      of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL 
      fusion) pointed the existence of dormant clone of normal residual hematopoietic 
      cells along with actively proliferating clones of Ph positive cells. Fluorescence 
      in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) 
      could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage 
      of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 
      patients had comparatively good prognosis (disease-free survival 7-14 months). Of 
      five patients with residual leukemic cells in the range of 2-6%, 4 relapsed 
      within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) 
      negative cells by CK] were evaluated by FISH to check the presence of residual 
      leukemic cells. In these patients FISH could efficiently detect 1-14.5% of 
      residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, 
      P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of 
      leukemic cells (5-11%) relapsed within a short period (1-7 months). On the 
      contrary, 5 of 7 patients with either absence or low percentage of PML-RARA 
      positive cells remained in complete remission for 11-24 months. Our data show 
      that FISH has a potential to detect and measure the fraction of aberrant 
      malignant cells in remission marrows, induced by BMT in CML and chemotherapy in 
      APL. These findings encourage the investigations on a large scale to merit its 
      potential for identification of patients at high risk. In the present studies, 
      FISH on interphase cells also demonstrated its efficiency in the molecular 
      diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with 
      masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of 
      technique in molecular diagnosis was also proved in one of the CML patients who 
      progressed to myeloid blastic phase where interphase FISH could identify an extra 
      BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its 
      duplication.
FAU - Amare, P S
AU  - Amare PS
AD  - Cytogenetics Laboratory, Department of Medical Oncology, Tata Memorial Hospital, 
      Parel, Mumbai-400012, India. pratibha@bom7.vsn1.net.in
FAU - Baisane, C
AU  - Baisane C
FAU - Saikia, T
AU  - Saikia T
FAU - Nair, R
AU  - Nair R
FAU - Gawade, H
AU  - Gawade H
FAU - Advani, S
AU  - Advani S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Female
MH  - Fusion Proteins, bcr-abl/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Karyotyping
MH  - Leukemia, Myeloid/*diagnosis/drug therapy/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/genetics
MH  - Oncogene Proteins, Fusion/genetics
MH  - Predictive Value of Tests
MH  - Sensitivity and Specificity
EDAT- 2001/12/26 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/12/26 10:00
PHST- 2001/12/26 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/12/26 10:00 [entrez]
AID - S0165460801005040 [pii]
AID - 10.1016/s0165-4608(01)00504-0 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2001 Dec;131(2):125-34. doi: 
      10.1016/s0165-4608(01)00504-0.