Nicoletta Sacchi

• Professor
• Professor (Full) at Roswell Park Comprehensive Cancer Center

All-trans retinoic acid (RA), which is the dietary bioactive derivative obtained from animal (retinol) and plant sources (beta-carotene), is a physiological lipid signal of both embryonic and postembryonic development. During pregnancy, either RA deficiency or an excessive RA intake is teratogenic. Too low or too high RA affects not only prenatal,...

Breast ductal carcinoma in situ (DCIS) has been typically recognized by pathologists on the basis of aberrant mammary duct morphology. Thus, there are increasing efforts to detect DCIS biomarkers and druggable targets. In this study we focused on the molecular mechanism involving Annexin A8 (ANXA8), a Ca2+ and phospholipid binding protein, which is...

The MYC transcription factor coordinates, via different RNA polymerases, the transcription of both ribosomal RNA (rRNA) and protein genes necessary for nucleolar as well as mitochondrial ribogenesis. In this study we tested if MYC-coordination of rRNA transcription in the nucleolus and in the mitochondrion drives (cancer) cell proliferation. Here w...

RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant...

Genetic and environmental factors cooperate to assure precise genome-wide epigenetic regulation of the mammary epithelia cell transcriptome. Our interest in regulatory epigenetic mechanisms that, by determining mammary epithelial cell decisions, are pivotal to deter the onset and progression of breast cancer, let us identify a regulatory epigenetic...

Upregulation of RNA Polymerase (Pol I)-mediated transcription of ribosomal RNA (rRNA) and increased ribogenesis, which are necessary to sustain the increased metabolic demand of highly proliferating cancer cells, are hallmarks of cancer. Increased rRNA transcription can be due deregulation of tumor suppressors and oncogenes that affect Pol I activi...

A hallmark of cancer cells is the ability to evade the growth inhibitory/pro-apoptotic action of physiological all-trans retinoic acid (RA) signal, the bioactive derivative of Vitamin A. However, as we and others reported, RA can also promote cancer cell growth and invasion. Here we show that anticancer and cancer-promoting RA actions in breast can...

Upregulation of RNA Polymerase (Pol I)-mediated transcription of ribosomal RNA (rRNA) and increased ribogenesis are hallmarks of breast cancer. According to several datasets, including the Cancer Genome Atlas (TCGA), amplification/upregulation of genes encoding for basal components of the Pol I transcriptional machinery is frequent at different bre...

All-trans retinoic acid (RA), the bioactive derivative of vitamin A, can paradoxically exert both anti-cancer and cancer-promoting actions. According to our studies, RA promotes breast cancer cell growth and invasion whenever it fails to exert its genome-wide epigenetic control of transcription via the RA receptor alpha (RARA). Factors that negativ...

Physiological retinoic acid (RA), the bioactive derivative of Vitamin A, is a signal necessary for epithelial cell morphogenesis. During acinar morphogenesis of normal breast epithelial cells in three dimensional (3D) culture, physiological RA activates in a spatiotemporal fashion both genomic and non-genomic RA receptor alpha (RARA) signalings, th...

The core binding factor (CBF) transcription factor complex regulates coding and non-coding genes that play a critical role in hematopoiesis. Chromosomal rearrangements involving the two CFB subunits, RUNX1 and CFB beta, are common in acute myeloid leukemia (AML). The fusion proteins resulting from these rearrangements deregulate the transcription o...

The core binding factor (CBF) complex plays a critical role in hematopoiesis by regulating the expression of both coding and non-coding RNAs. Nonrandom cytogenetic rearrangements involving either one of the CFB subunits, CBF alpha (also known as RUNX1) and CFB beta (CBFB), in myeloid cells define a specific subgroup of acute myelogenous leukemia, t...

Background Core Binding Factor acute myeloid leukemia (CBF-AML) with t (8;21) RUNX1-MTG8 or inv (16) CBFB-MYH11 fusion proteins often show upregulation of wild type or mutated KIT receptor. However, also non-CBF-AML frequently displays upregulated KIT expression. In the first part of this study we show that KIT expression can be also upregulated by...

Core Binding Factor acute myeloid leukemia (CBF-AML) with t(8;21) RUNX1-MTG8 or inv(16) CBFB-MYH11 fusion proteins often show upregulation of wild type or mutated KIT receptor. However, also non-CBF-AML frequently displays upregulated KIT expression. In the first part of this study we show that KIT expression can be also upregulated by miR-17, a re...

Endogenous retinoic acid (RA), the bioactive derivative of Vitamin A, is necessary for breast acinar morphogenesis. One of the hallmarks of early stage breast cancer, such as ductal carcinoma in situ (DCIS), is the inability to respond to RA morphogenetic action, which results in the uncontrolled growth of the mammary duct luminal cells. By imaging...

It is estimated that up to 90% of women have benign breast lesions, some of which are pre-malignant. In situ lesions, particularly the ones that involve the ducts (ductal carcinoma in situ, DCIS), have the potential to progress into invasive malignant lesions and become life threatening. These breast premalignant states are identified because of sp...

Altered estrogen receptor alpha (ERA) signaling and altered circadian rhythms are both features of breast cancer. ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells (Rossetti et al., 2012a). Interestingly, we identified a circuit consisting of ERA and an estrogen-regulated...

Hematopoietic development is orchestrated by gene regulatory networks that progressively induce lineage-specific transcriptional programs. To guarantee the appropriate level of complexity, flexibility, and robustness, these networks rely on transcriptional and post-transcriptional circuits involving both transcription factors (TFs) and microRNAs (m...

Hematopoietic development is orchestrated by gene regulatory networks that progressively induce lineage-specific transcriptional programs. To guarantee the appropriate level of complexity, flexibility, and robustness, these networks rely on transcriptional and post-transcriptional circuits involving both transcription factors (TFs) and microRNAs (m...

Altered estrogen receptor α (ERA) signaling and altered circadian rhythms are both features of breast cancer. By using a method to entrain circadian oscillations in human cultured cells, we recently reported that the expression of key clock genes oscillates in a circadian fashion in ERA-positive breast epithelial cells but not in breast cancer cell...

Most physiological and biological processes are regulated by endogenous circadian rhythms under the control of both a master clock, which acts systemically and individual cellular clocks, which act at the single cell level. The cellular clock is based on a network of core clock genes, which drive the circadian expression of non-clock genes involved...

Preformed vitamin A, or Retinol, is found in animal foods, such as liver and whole milk, and in some fortified food products. Carotenoids, such as beta-carotene from fruit and vegetables, are also efficiently converted into Retinol. Retinol, once converted into its bioactive form, retinoic acid (RA), plays a major role in cell division, cell death,...

Core-binding factor leukemia (CBFL) is a subgroup of acute myeloid leukemia (AML) characterized by genetic mutations involving the subunits of the core-binding factor (CBF). The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for...

Preformed vitamin A, or Retinol, is found in animal foods, such as liver and whole milk, and in some fortified food products. Carotenoids, such as beta-carotene from fruit and vegetables, are also efficiently converted into Retinol. Retinol, once converted into its bioactive form, retinoic acid (RA), plays a major role in cell division, cell death,...

Human MTG16a (CBFA2T3), a chromatin repressor with nucleolar localization, was described to act as a suppressor of breast tumourigenesis. Here we show that MTG16a is a novel ribosomal gene repressor, which can counteract MYC-driven activation of ribosomal RNA (rRNA) transcription. We also show that either knocking down MTG16a by RNA interference, o...

Objectives: Preformed vitamin A, or Retinol, is found in animal foods such as liver and whole milk and in some fortified food products. Carotenoids such as beta-carotene from fruit and vegetables are also efficiently converted into Retinol. Retinol converted into its bioactive form retinoic acid (RA) plays a major role in cell division, cell death...

In silico identification of human CYP26A1 CpG islands. Analysis of the CYP26A1 5′ regulatory regions by using CpG Island Searcher identifies two CpG islands: one containing the distal RARE (D-RARE), from −2086 to −1502, and one containing the proximal RARE (P-RARE), from −375 to +2239. (9.31 MB TIF)

Development of CRABP2 knock down clones. (A) Scheme of the short hairpin (sh) RNA sequences cloned into the pSUPER vector and subsequently used for HME1 stable transfection (left). Transient co-transfection experiments followed by WB analysis showing that the CRABP2-targeting sequences CRABP2-A and CRABP2-C, but not the scrambled sequence Mock, can...

CYP26A1 downregulation in human cells with an impaired RA-RARα signaling is marked by epigenetic chromatin changes. (A) Hampering RA availability at RARα by treatment with the RARα-specific antagonist ER50891 can significantly antagonize RA-induced transcription of both RARβ2 (top) and CYP26A1 (bottom) in human cells (T47D). (B) T47D cells stably e...

Chromatin adapts and responds to extrinsic and intrinsic cues. We hypothesize that inheritable aberrant chromatin states in cancer and aging are caused by genetic/environmental factors. In previous studies we demonstrated that either genetic mutations, or loss, of retinoic acid receptor alpha (RARalpha), can impair the integration of the retinoic a...

s: Frontiers in Cancer Prevention Research 2008 A19 RARB2 is a master tumor suppressor that mediates the growth-inhibitory action of retinoic acid (RA). Homozygosis for epigenetically silent RARB2 alleles, which results into loss of RARB2 tumor suppressor activity, leads to RA-resistance, and apparently precedes the acquisition of morphological...

RARB2 is a master tumor suppressor that mediates the growth-inhibitory action of retinoic acid (RA). Homozygosis for epigenetically silent RARB2 alleles, which results into loss of RARB2 tumor suppressor activity, leads to RA-resistance, and apparently precedes the acquisition of morphological transformation of breast epithelial cells (Bistulfi et...

The myeloid translocation gene (MTG) proteins are non-DNA-binding transcriptional regulators capable of interacting with chromatin modifying proteins. As a consequence of leukemia-associated chromosomal translocations, two of the MTG proteins, MTG8 and MTG16, are fused to the DNA-binding domain of AML1, a transcriptional activator crucial for hemat...

Exposure to artificial light correlates with higher incidence of breast cancer. Shift workers, whose day/night rhythms are altered by their odd hours, appear more prone to develop breast cancer. In response to natural light, a master clock in our brain regulates molecular clocks in cells of the peripheral tissues, triggering clock-regulated genes t...

Resveratrol exerts a drastic growth inhibitory effect on human breast cancer MDA-MB-231 cells grown both in vitro and in vivo. Here we show that resveratrol affects the aggregation properties of MDA-MB-231 cells into multicellular tumor spheroids (MCTSs), in association with induction of de novo synthesis of ceramide. After 9 days of 3D growth in t...

An altered morphology of the nucleolus and aberrant transcription of nucleolar ribosomal genes is common in breast cancer. We previously demonstrated that MTG16, a transcriptional repressor protein whose expression is frequently down regulated/lost in breast cancer can localize both in the nucleus and in the nucleolus. When we stably knocked down M...

Vitamin A or retinol, and its bioactive derivative retinoic acid (RA), are used as chemoprevention or chemotherapy in some human cancers. However, paradoxically, both retinol and RA were also found to exert tumor promoting effects. Recently, we found that human breast cancer cells where we induced functional inhibition of RA receptor alpha (RARA) d...

Retinoic acid (RA), the bioactive derivative of vitamin A, is a pleiotropic signaling molecule that plays a key role in cell proliferation, differentiation and apoptosis. RA exerts its effects mainly by modulating gene transcription through the retinoic acid receptors, RARs. Upon RA binding, one of these receptors, RAR alpha (RARA), can activate th...

Human myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG16, the fusi...

Evidence of functional AML1 haploinsufficiency in AML1-MTG16-expressing cells. This figure shows the Ingenuity Pathways Analysis of the global gene expression changes identified in AML1-MTG16-expressing cells.

Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-re...

Background: Human myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG...

Retinoic acid (RA) is a master epigenetic regulator that plays a pivotal role in both breast morphogenesis and development. Here, we show for the first time that RA, via the RA receptor alpha (RARalpha), epigenetically regulates in a concerted fashion the transcription of two RA-responsive genes, the RA receptor beta2 (RARbeta2) and the cellular re...

MTG16 belongs to a family of evolutionary conserved proteins, can act as an oncogene in leukemia and as a tumor suppressor in breast cancer cells. We found that MTG16 binds histone deacetylases, acts as a corepressor in chromatin-regulated gene transcription, and localizes both in the nucleus and the nucleolus. Consistently, MTG16a binds the promot...

Retinoic acid (RA), the bioactive derivative of vitamin A, is a potent inhibitor of cell growth. RA action is mediated by the RA-receptors. We found that induction of RARb2 epigenetic silencing in RA-sensitive breast cancer cells, make them susceptible to become growth promoted by RA (Ren et al., Mol Cell Biol, 2005). Further, we observed that this...

Since its introduction, the 'single-step' method has become widely used for isolating total RNA from biological samples of different sources. The principle at the basis of the method is that RNA is separated from DNA after extraction with an acidic solution containing guanidinium thiocyanate, sodium acetate, phenol and chloroform, followed by centr...

Resistance to the growth-inhibitory action of retinoic acid (RA), the bioactive derivative of vitamin A, is common in human tumors. One form of RA resistance has been associated with silencing and hypermethylation of the retinoic acid receptor β2 gene (RARβ2), an RA-regulated tumor suppressor gene. The presence of an epigenetically silent RARβ2 cor...

Resveratrol, a natural product with a stilbene structure, exerts profound proapoptotic activity in human cancer cells, by triggering the accumulation of ceramide, a bioactive sphingolipid. We studied the biological effects of seven methoxylated and/or naphthalene-based resveratrol analogues and compared these compounds with resveratrol with the obj...

De novo epigenetic changes at histone and DNA level that affect gene transcription in cancer may be less random than we originally thought. Leukemia fusion proteins associated with specific chromosome translocations could mechanistically determine the epigenetic fate of specific target genes critical for normal hematopoiesis. This seems to be the c...

In retinoid resistant epithelial tumors, the lack of retinoic acid receptor beta2 (RARbeta2) expression due to epigenetic silencing impairs the activation of retinoid target genes including RARbeta2, and has been associated with the development of cancer. In this study we developed a strategy to monitor the re-activation of RARbeta2 by chromatin re...

The human ETS2 and ERG genes are members of the ETS gene family, with sequence homology to the viral ets gene of the avian erythroblastosis retrovirus, E26. These genes are located on chromosome 21 and molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 suggested that ETS2 may be a gene within the minimal DS genetic re...

Sphingolipids, a family of membrane lipids, play not only a structural role, but can also act as effector molecules in a variety of cell processes. We recently reported that retinoic acid (RA) controls the metabolism of the biologically active sphingolipids, ceramide and sphingosine-1-phosphate in breast cancer cells through RA-receptors (RARs). As...

Retinoic acid (RA), the bioactive derivative of dietary Vitamin A, is essential for the maintenance of epithelial growth and differentiation. As such, it was used for chemoprevention of epithelial carcinogenesis and in differentiation therapy. RA controls gene expression through liganddependent transcription factors called retinoic acid receptors (...

Bamboo grass leaves of different Sasa species have been widely used in food and medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa Health. This extract was reported to inhibit both the development and growth of mammary tumors in a mammary...

The human myeloid translocation genes (MTGs) encode a family of proteins with a modular structure that can be traced to the Drosophila protein nervy. The nuclear MTGs can mediate the formation of complex protein networks among nuclear corepressors (Sin3a, N-CoR, SMRT), chromatin-modifying enzymes (histone deacetylases), and DNA-binding transcriptio...

Most often it is not the primary tumor, but metastasis to distant organs that results in the death of breast cancer patients. To characterize molecular alterations in breast cancer metastasis, we investigated the frequency of hypermethylation of five genes (Cyclin D2, RAR-beta, Twist, RASSF1A, and HIN-1) in metastasis to four common sites: lymph no...

Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogen...

Retinoic acid (RA) resistance is a major hurdle of retinoid-differentiation therapy. One form of RA-resistance in breast cancer can be traced to loss of expression of the tumor suppressor RAR beta, due to epigenetic changes including DNA methylation and histone deacetylation in one of the RAR beta promoters. Epigenetic changes are reversible. By us...

Resveratrol (3,4',5-trans-trihydroxystilbene) is a dietary polyphenol with chemopreventive properties present in grapes, red wine, peanuts and other edible products. The antiproliferative and proapoptotic effect of resveratrol in breast cancer cells can be traced to the accumulation of ceramide. In this study we demonstrate that resveratrol can als...

The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped to the MTG16a N-terminal region...

Loss of expression of retinoic acid receptor beta2 (RARbeta2), a potent tumor suppressor gene, is commonly observed during breast carcinogenesis. RARbeta2 silencing can be traced to epigenetic chromatin changes affecting the RARbeta P2 promoter. Here we show that retinoic acid therapy fails to induce RARbeta2 in primary breast tumors, which carry a...

The MTG8 (ETO/CDR), MTGR1 and MTG16 oncoproteins with a very high degree of sequence similarity with the Drosophila nervy are a novel family of transcriptional repressor molecules implicated in human leukemia and neurodegenerative disorders. Two of these proteins, MTG8 and MTG16, are found fused to AML1, one of the subunits of the hematopoietic cor...

Most procedures for isolating RNA from eukaryotic cells involve lysing and denaturing cells to liberate total nucleic acids. Additional steps are then required to remove DNA. The first basic protocol describes hot phenol extraction of RNA; the method eliminates or minimizes DNA contamination by the shearing of DNA. The second basic protocol allows...

Most procedures for isolating RNA from eukaryotic cells involve lysing and denaturing cells to liberate total nucleic acids. Additional steps are then required to remove DNA. The first basic protocol describes hot phenol extraction of RNA; the method eliminates or minimizes DNA contamination by the shearing of DNA. The second basic protocol allows...

Three different methods for RNA preparation using guanidine are presented in this unit--a single-step isolation method employing liquid-phase separation to selectively extract total RNA from tissues and cultured cells and two methods that rely on a CsCl step gradient to isolate total RNA.

If detected early, breast cancer is curable. We tested cells collected from the breast ducts by methylation-specific PCR (MSP). Methylated alleles of Cyclin D2, RAR-beta, and Twist genes were frequently detected in fluid from mammary ducts containing endoscopically visualised carcinomas (17 cases of 20), and ductal carcinoma in situ (two of seven),...

We have isolated and characterised one PAC clone (dJ233C1) containing a linkage between alphoid and non-alphoid DNA. The non-alphoid DNA was found to map at the pericentromeric region of chromosome 20, both on p and q sides, and to contain homologies with one contig (ctg176, Sanger Centre), also located in the same chromosome region. At variance wi...

Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family of neurodegenerative diseases caused by expansion of a polyglutamine tract. The drpla gene product, atrophin-1, is widely expressed, has no known function or activity, and is found in both the nuclear and cytoplasmic compartments of neurons. Truncated fragments of atrophin-1 ac...

The search of chemopreventive strategies for breast cancer is imperative. It is vital to identify critical early events that can increase the risk that a normal epithelial mammary cell may be transformed into a breast cancer cell. Exposure to estrogen, already, recognized as a predisposing event for breast cancer, formed the rationale for preventiv...

Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of th...

Retinoic acid (RA)-resistance in breast cancer cells has been associated with irreversible loss of retinoic acid receptor beta, RARbeta, gene expression. Search of the causes affecting RARbeta gene activity has been oriented at identifying possible differences either at the level of one of the RARbeta promoters, RARbeta2, or at regulatory factors....

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed...

The t(8;21) translocation associated with acute myeloid leukemia (AML) disrupts two genes, the AML1 gene also known as the core binding factor A2 (CBFA2) on chromosome 21, and a gene on chromosome 8, hereafter referred to as MTG8, but also known as CDR and ETO. Extensive information is available on AML1, a member of the CBF family of transcription...

The translocation (8;21) is a chromosome abnormality associated with acute myeloid leukemia (AML). As a consequence of the translocation the AML1 (CBFA2) gene in the 21q22 region is fused to the ETO(CDR,MTG8) gene in the 8q22 region, resulting in one transcriptionally active gene on the 8q- derivative chromosome. In this report we demonstrate the u...

Bone marrow from six patients with acute myeloid leukemia (AML) and t(8;21) (q22;q22) or a variant t(8;13;21) was studied by simultaneous analysis of cell morphology and karyotype. Combination of May-Grünwald-Giemsa (MGG) and fluorescence in situ hybridization (FISH) using probes specific for the breakpoint regions of chromosome 8 and 21 allowed us...

Truncated AML1 proteins are predicted to be expressed from out-of-frame AML1 transcripts present in myeloid leukemia cells harboring t(8;21) and t(3;21). To test whether these proteins, consisting of almost exclusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar truncated AML1 protein in 32D...

AML1, a gene encoding a protein of the PEBP2/CBF family of transcription factors is disrupted by translocations associated with human leukemia. In the t(8;21) acute myelogenous leukemia (AML), AML1 was found fused to a gene on chromosome 8 that we designated CDR (also known as ETO and MTG8). Immunoprecipitation experiments followed by immunoblottin...

Centromere activation, an important mechanism in karyotype evolution, is occasionally observed in some human chromosome rearrangements. We report a possible occurrence of centromere activation in a marker chromosome containing an atypical centromere associated with an inverted duplication of the region 14q32 --> qter. The marker chromosome's reduce...

In the translocation (8;21)(q22;q22) associated with acute myelogenous leukemia (AML), part of the long arm of chromosome 8 is reciprocally translocated onto chromosome 21. At the molecular level the translocation results in the fusion of the 5' region of the AML1 gene on chromosome 21 and almost the entire CDR gene (also ETO or MTG8) on chromosome...

Fluorescence in situ hybridization (FISH) and/or RNA-based polymerase chain reaction (RT-PCR) were used to analyze the breakpoints within the AML1 gene and the AML1 fusion transcripts in t(8;21) acute myeloid leukemia (AML). Twenty-two patients presented with the simple t(8;21)(q22;q22) and one with a complex variant t(8;2;16;21). In eight cases we...

The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and with leukemia following other hematopoietic proliferative diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even w...

The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and with leukemia following other hematopoietic proliferate diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even wit...