Test ID: FIMRG
Imatinib Mesylate Responsive Genes, Locus Anomalies, FISH

Detecting a neoplastic clone associated with the common chromosome anomalies seen in patients with acute leukemia or other myeloid malignancies

Tracking known chromosome abnormalities in patients with myeloid malignancies thus assessing their response to therapy. 

This panel is particularly useful for specimens in which standard cytogenetic analysis is unsuccessful.

Panel includes testing for the following anomalies via the probes listed:

ABL2/1q25, BAP ABL2

CHIC2/4q12, FIP1L1 CHIC2 PDGFRA

PDGFRB/5q33, BAP PDGFRB

ABL1/9q34, BAP ABL1

If the patient is being tracked for known anomalies, indicate which anomalies need to be investigated.

When this test is ordered, a charge for 2 FISH probes and interpretation is included. If additional probes or the entire panel are ordered, additional probe charges will be added.

• Cytogenetics Hematologic FISH Panel Patient Information Sheet

Fluorescence In Situ Hybridization (FISH)

Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

Forms: 

1. Cytogenetics Hematologic FISH Panel Patient Information Sheet (Supply T603) in Special Instructions

2. If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.

Submit only 1 of the following specimens:

Specimen Type: Blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 5 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

Specimen Type: Bone marrow

Container/Tube: Green top (sodium heparin)

Specimen Volume: 1-2 mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

Myeloid neoplasms are primary disorders of the bone marrow cells. These malignancies encompass several entities with extremely varied clinical courses, including acute myeloid leukemias (AML), chronic myeloproliferative disorders (CMPD), and myelodysplastic syndromes. The underlying genetic mechanisms associated with these malignancies are varied and only a portion of the genetic anomalies have targeted therapies clinically available.

One group of genes, including ABL1 (Abelson murine leukemia viral oncogene homolog 1), ABL2 (Abelson murine leukemia viral oncogene homolog 2), PDGFRA (platelet-derived growth factor receptor, alpha), and PDGFRB (platelet-derived growth factor receptor, beta) can be inappropriately activated via various genetic mechanisms and result in overexpression of their tyrosine kinase activity. Tyrosine kinase activity plays an important role in cellular signaling, division, and differentiation; overexpression may cause some cancers. The myeloid malignancies associated with these aberrantly expressed genes include AML, chronic myelogenous leukemia (CML), hypereosinophilic syndrome/systemic mast cell disease (HES/SMCD), and atypical CMPD. These translocations can also be seen in lymphoid neoplasms, including acute lymphoblastic leukemia (ALL) and lymphomas, and they can also possess a varied genetic etiology. Several clinical studies have demonstrated that the malignancies displaying overexpression of these genes are responsive to imatinib mesylate (Gleevec), a drug that specifically targets these genes.

An interpretive report will be provided.

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for any given probe.

The presence of a positive clone supports a diagnosis of malignancy.

The absence of an abnormal clone does not rule out the presence of neoplastic disorder.

This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs for each probe were calculated based on the results of at least 20 normal specimens. For each probe set, a series of chromosomally abnormal specimens were evaluated to confirm that each probe set detected the anomaly it was designed to detect.

1. Trempat P, Villalva C, Laurent G, et al: Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor; a new clinical target for STI571/Glivec. Oncogene 2003 Aug 28;22(36):5702-5706

2. Dave BJ, Wiggins M, Higgeins CM, et al: 9q34 rearrangements in BCR/ABL fusion-negative acute lymphoblastic leukemia. Cancer Genet Cytogenet 2005 Oct 1;162:30-37

3. Pardanani A, Reeder T, Porrata LF, et al: Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders. Blood 2003 May 1;101(9):3391-3397

4. Pardanani A, Tefferi A: Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders. Blood 2004 Oct 1;104(7):1931-1939

Identification of rearrangements of 1q25 (ABL2), 9q34 (ABL1), 5q33 (PDGFRB), and 4q12 (CHIC2 - FIP1L1 and PRGFRA fusion result in a loss of the CHIC2 locus), is performed using FISH break-apart strategy. For each probe set, 200 interphase nuclei are scored. Results for each abnormal probe is expressed as percent abnormal nuclei. (Brockman SR, Paternoster SF, Ketterling RP, et al: New highly sensitive fluorescence in situ hybridization method to detect PML/RARA fusion in acute promyelocytic leukemia. Cancer Genet Cytogenet 2003;145:144-151)

Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.

Imatinib Mesylate Responsive Genes, Locus Anomalies, FISH

88271 x 2-DNA probe, each

88275-Interphase in situ hybridization

88291-Interpretation and report

One Additional FISH Probe

88271-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Two Additional FISH Probes

88271 x 2-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Three Additional FISH Probes

88271 x 3-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Four Additional FISH Probes

88271 x 4-DNA probe, each (if appropriate)

88275 x 2-Interphase in situ hybridization (if appropriate)

Five Additional FISH Probes

88271 x 5-DNA probe, each (if appropriate)

88275 x 2-Interphase in situ hybridization (if appropriate)

Six Additional FISH Probes

88271 x 6-DNA probe, each (if appropriate)

88275 x 3-Interphase in situ hybridization (if appropriate)

Seven Additional FISH Probes

88271 x 7-DNA probe, each (if appropriate)

88275 x 3-Interphase in situ hybridization (if appropriate)

Eight Additional FISH Probes

88271 x 8-DNA probe, each (if appropriate)

88275 x 4-Interphase in situ hybridization (if appropriate)

Nine Additional FISH Probes

88271 x 9-DNA probe, each (if appropriate)

88275 x 4-Interphase in situ hybridization (if appropriate)

Ten Additional FISH Probes

88271 x10-DNA probe, each (if appropriate)

88275 x 5-Interphase in situ hybridization (if appropriate)

Eleven Additional FISH Probes

88271 x 11-DNA probe, each (if appropriate)

88275 x 5-Interphase in situ hybridization (if appropriate)

Twelve Additional FISH Probes

88271 x 12-DNA probe, each (if appropriate)

88275 x 6-Interphase in situ hybridization (if appropriate)

Thirteen Additional FISH Probes

88271 x 13-DNA probe, each (if appropriate)

88275 x 6-Interphase in situ hybridization (if appropriate)

Fourteen Additional FISH Probes

88271 x 14-DNA probe, each (if appropriate)

88275 x 7-Interphase in situ hybridization (if appropriate)

Fifteen Additional FISH Probes

88271 x 15-DNA probe, each (if appropriate)

88275 x 7-Interphase in situ hybridization (if appropriate)

Sixteen Additional FISH Probes

88271 x 16-DNA probe, each (if appropriate)

88275 x 8-Interphase in situ hybridization (if appropriate)

Seventeen Additional FISH Probes

88271 x 17-DNA probe, each (if appropriate)

88275 x 8-Interphase in situ hybridization (if appropriate)

Eighteen Additional FISH Probes

88271 x 18-DNA probe, each (if appropriate)

88275 x 9-Interphase in situ hybridization (if appropriate)

Nineteen Additional FISH Probes

88271 x 19-DNA probe, each (if appropriate)

88275 x 9 Interphase in situ hybridization (if appropriate)

Twenty Additional FISH Probes

88271 x 20-DNA probe, each (if appropriate)

88275 x 10-Interphase in situ hybridization (if appropriate)

Twenty One Additional FISH Probes

88271 x21-DNA probe, each (if appropriate)

88275 x10-Interphase in situ hybridization (if appropriate)

Twenty Two Additional FISH Probes

88271 x22-DNA probe, each (if appropriate)

88275 x11-Interphase in situ hybridization (if appropriate)

Twenty Three Additional FISH Probes

88271 x23-DNA probe, each (if appropriate)

88275 x11-Interphase in situ hybridization (if appropriate)

Twenty Four Additional FISH Probes

88271 x24-DNA probe, each (if appropriate)

88275 x12-Interphase in situ hybridization (if appropriate)

Twenty Five Additional FISH Probes

88271 x25-DNA probe, each (if appropriate)

88275 x12-Interphase in situ hybridization (if appropriate)

Twenty Six Additional FISH Probes

88271 x26-DNA probe, each (if appropriate)

88275 x13-Interphase in situ hybridization (if appropriate)

Twenty Seven Additional FISH Probes

88271 x27-DNA probe, each (if appropriate)

88275 x13-Interphase in situ hybridization (if appropriate)

Twenty Eight Additional FISH Probes

88271 x28-DNA probe, each (if appropriate)

88275 x14-Interphase in situ hybridization (if appropriate)

Twenty Nine Additional FISH Probes

88271 x29-DNA probe, each (if appropriate)

88275 x14-Interphase in situ hybridization (if appropriate)

Thirty Additional FISH Probes

88271 x30-DNA probe, each (if appropriate)

88275 x15-Interphase in situ hybridization (if appropriate)