B-Cell Acute Lymphoblastic Leukemia (ALL), FISH
As an adjunct to conventional chromosome studies in patients with acute lymphoblastic leukemia (ALL), especially:
-When conventional chromosome studies do not demonstrate a classic chromosome anomaly
-For pediatric patients
-When results for conventional chromosome studies are normal or unavailable because of an unsuccessful study
Detecting clones with t(1;19), t(9;22), t(12;21), t(11;var), t(14;var), del(9p), +4, +10, or +17
Quantifying disease before and after treatment for patients with ALL
Assessing residual disease after treatment (in this situation, it is cost effective to order only those FISH probes that produced abnormal results prior to treatment)
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Precursor B-cell acute lymphoblastic leukemia (ALL) accounts for 85% of children and 20% of adults who have acute leukemia. Most patients with ALL have an abnormal clone by conventional cytogenetic studies, and at least 36 chromosome anomalies are common in this disorder.(1) The most common karyotype among children with ALL is hyperdiploidy, which is associated with a good prognosis in the absence of any structural anomalies and when associated with trisomies of chromosomes 4, 10, and 17. The most common chromosome translocations in pediatric ALL include t(9;22)(q34;q11.2), t(12;21)(p13;q22), t(1;19)(q23;p13), t(8;14)(q24;q32), t(14;var)(q32;var), and t(11;var)(q23;var). The t(12;21)(p13;q22) is associated with ETV6/RUNX1 fusion and is impossible to detect by conventional cytogenetic studies. This translocation, along with other common translocations, can be successfully detected by FISH.
All of these translocations are important to detect as they are critical prognostic markers. The decision for early transplantation may be made if t(9;22)(q34;q11.2) is detected. In contrast, if t(12;21)(p13;q22) or ETV6/RUNX1 fusion is detected, the patient has an excellent prognosis and transplantation is rarely considered. Deletions of chromosome 9 p-arm are also common, though the clinical significance of this finding is still uncertain.
Cytogenetic and/or FISH testing is critical in the workup of patients with ALL to ensure the most appropriate treatment.(2) We recommend the following testing for patients with ALL(1):
-At diagnosis, conventional cytogenetic studies (eg, BM/8506 Chromosome Analysis, Hematologic Disorders, Bone Marrow) should be performed, especially for pediatric individuals, where solely numeric anomalies occur in 25% of patients.
-FISH is valuable in some cases to detect certain cryptic chromosome anomalies such as ETV6/RUNX1 fusion associated with t(12;21)(p12;q22).
-FISH studies should be done at diagnosis whenever results of chromosome studies do not demonstrate a classical chromosome anomaly (ie, chromosome studies are normal or complex); FISH studies should also be considered when results of chromosome studies are unsuccessful.
-FISH can be performed at diagnosis and after treatment to establish a benchmark for the percentage of neoplastic cells to help assess the effectiveness of therapy.
-If the patient relapses, a conventional chromosome study is useful to identify prognostic changes in the neoplastic clone and identify any newly arisen clones.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report is provided.
A neoplastic clone is detected when the percent of cells with any given chromosome abnormality exceeds the normal cutoff. This method detects neoplastic clones with chromosome abnormalities in more than 80% of patients with acute lymphoblastic leukemia.
Disease can be quantified by determining the percentage of cells demonstrating anomalies. The effect of treatment can be assessed by comparing the percentage of cells demonstrating anomalies before and after therapy.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
FISH is not a substitute for conventional chromosome studies because the latter detects many chromosome anomalies associated with other hematological disorders that would be missed by this FISH panel test.
We used a state-of-the-art panel FISH test to evaluate a series of consecutive specimens referred to our laboratory for conventional chromosome studies between 1990 and 2003. This study was done on bone marrow from 25 normal individuals and 62 patients with possible ALL. The patients included 22 females and 40 males; ages ranged from 2 to 31 years (median 5 years). Each patient received conventional chromosome studies for an acute leukemia clinical trial. Conventional chromosome studies were abnormal for 43 (69.4%) patients, FISH was abnormal for 51 (82.3%), and cytogenetics and FISH were abnormal for 52 (83.9%). In 1 case, FISH was normal, but conventional chromosome studies detected a neoplastic abnormal clone with abnormalities that could not be detected with our FISH probes. A total of 83 anomalies were detected among the 51 FISH abnormal patients: 1 (1.2%) BCR/ABL1 fusion, 3 (3.6%) PBX1/TCF3 fusion, 22 (26.5%) ETV6/RUNX1 fusion, 15 (18.1%) loss of CDKN2A, 12 (14.5%) trisomy 4, 10, and/or 17, and 30 (36.1%) other aneuploidies. Results of conventional chromosome studies and FISH were concordant for 29 specimens (46.8%) and discordant for 33 (53.2%). Discordance was predominantly associated with FISH detection of ETV6/RUNX1 fusion, deletion of CDKN2A, and various aneuploidies that were classified as markers or missed by conventional chromosome studies.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Dewald GW, Ketterling RP: Conventional cytogenetics and molecular cytogenetics in hematological malignancies. In Hematology. Basic Principles and Practice. 4th edition. Edited by R Hoffman, E Benz, S Shattil, et al. Philadelphia, Churchill Livingston, 2005, pp 928-939
2. Pui CH, Relling MV, Downing JR: Acute lymphoblastic leukemia. N Engl J Med 2004 Apr;350(15):1535-1548